Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function

Paradee, W.; Melikian, H.E.; Rasmussen, D.L.; Kenneson, A.; Conn, P.J.; Warren, S.T.

doi:10.1016/s0306-4522(99)00285-7

Cited by 305Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function

Paradee, W., Melikian, H.E., Rasmussen, D.L., Kenneson, A., Conn, P.J., Warren, S.T.·1999·Neuroscience

DOI 10.1016/s0306-4522(99)00285-7

Open this paper in CoChat — free account

Abstract

Fragile X syndrome is an X-linked form of mental retardation resulting from the absence of expression of the fragile X mental retardation 1 gene. The encoded protein is a ribosome-associated, RNA-binding protein thought to play a role in translational regulation of selective messenger RNA transcripts. A knockout mouse has been described that exhibits subtle deficits in spatial learning but normal early-phase long-term potentiation. We expanded these studies by examination of late-phase hippocampal long-term potentiation, the protein synthesis-dependent form of long-term potentiation, in the Fmrl knockout mice. Here, late-phase long-term potentiation was normal, suggesting either that absence of fragile X mental retardation protein has no influence on long-term potentiation or that any influence is too subtle to be detected by this technique. Alternatively, the hippocampus may not be the primary site affected by the absence of this protein. Accordingly, we examined spatial learning in the knockout mice using the hippocampus-dependent Morris water maze. Contrary to earlier reports, near-normal performance was observed. Since the knockout line used in this study has been back-crossed to C57BL/6 for more than 15 generations, whereas the line used in the earlier studies contained a substantial strain 129 contribution, we examined F1 siblings of knockout and 129 crosses. Here, significant but subtle increased swim latencies in reversal trials were observed, in agreement with the previous studies. These data suggest strain differences between C57BL/6 and 129 that influence the Fmrl knockout phenotype. In order to investigate a paradigm less dependent on hippocampal function, the knockout mice were examined using the conditional fear paradigm. Here, the knockout animals displayed significantly less freezing behavior than their wild-type littermates following both contextual and conditional fear stimuli. These data suggest that amygdala disturbances may also be involved in fragile X syndrome.

Integrity signals

Registry

Crossref · 10.1016/s0306-4522(99)00285-7

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The behavioral and cognitive deficits of Fmr1 KO mice are actually quite subtle and parallel Fragile X syndrome patients.
“By most accounts Fmr1 KO mice appear to have relatively normal behavior, but research has shown that the behavioral and cognitive deficits of the KO are actually quite subtle and parallel FXS patients (Berry-Kravis et al., 2002; D’Hooge et al., 1997; Paradee et al., 1999; Peier et al., 2000).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Paradee et al., 1999

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481 · see citing works
Self-citation
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Spatial localization does not require the presence of local cues
Morris, R. G. M. (1981) · Learning and Motivation · doi:10.1016/0023-9690(81)90020-5 · Cited by 2,699 · see citing works
Synaptic tagging and long-term potentiation
Frey, U., & Morris, R. G. M. (1997) · Nature · doi:10.1038/385533a0 · Cited by 1,736 · see citing works
Emotion: Clues from the Brain
LeDoux, J. E. (1995) · Annual Review of Psychology · doi:10.1146/annurev.ps.46.020195.001233 · Cited by 1,646 · see citing works
Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M. F., & Mandel, J. L. (1991) · Science · doi:10.1126/science.252.5009.1097 · Cited by 1,499 · see citing works
Absence of expression of the FMR-1 gene in fragile X syndrome
Pieretti, M., Zhang, F., Fu, Y.-H., Warren, S. T., Oostra, B. A., Caskey, C. T., & Nelson, D. L. (1991) · Cell · doi:10.1016/0092-8674(91)90125-i · Cited by 1,476 · see citing works
Deficient Hippocampal Long-Term Potentiation in α-Calcium-Calmodulin Kinase II Mutant Mice
Silva, A. J., Stevens, C. F., Tonegawa, S., & Wang, Y. (1992) · Science · doi:10.1126/science.1378648 · Cited by 1,472 · see citing works
Short-Term Synaptic Plasticity
Zucker, R. S. (1989) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.12.030189.000305 · Cited by 1,450 · see citing works
Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies
Crawley, J. N., Belknap, J. K., Collins, A. C., Crabbe, J. C., Frankel, W. N., Henderson, N. D., HITZEMANN, R. J., Maxson, S. C., Miner, L. L., Silva, A. J., et al. (1997) · Psychopharmacology · doi:10.1007/s002130050327 · Cited by 1,372 · see citing works
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,075 · see citing works
Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5401 · Cited by 1,046 · see citing works
Requirement of a Critical Period of Transcription for Induction of a Late Phase of LTP
Nguyen, P. V., Abel, T., & Kandel, E. R. (1994) · Science · doi:10.1126/science.8066450 · Cited by 888 · see citing works
Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro
Frey, U., Krug, M., Reymann, K. G., & Matthies, H. (1988) · Brain Research · doi:10.1016/0006-8993(88)90008-x · Cited by 806 · see citing works
FMR1 Protein: Conserved RNP Family Domains and Selective RNA Binding
Ashley, C. T., Wilkinson, K. D., Reines, D., & Warren, S. T. (1993) · Science · doi:10.1126/science.7692601 · Cited by 741 · see citing works
Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice
Simpson, E. M., Linder, C. C., Sargent, E. E., Davisson, M. T., Mobraaten, L. E., & Sharp, J. J. (1997) · Nature Genetics · doi:10.1038/ng0597-19 · Cited by 686 · see citing works
DNA methylation represses FMR-1 transcription in fragile X syndrome
Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D., & Warren, S. T. (1992) · Human Molecular Genetics · doi:10.1093/hmg/1.6.397 · Cited by 680 · see citing works
Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear.
Kim, J. J., Rison, R. A., & Fanselow, M. S. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.6.1093 · Cited by 615 · see citing works
Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events
Larson, J., & Lynch, G. (1986) · Science · doi:10.1126/science.3704635 · Cited by 597 · see citing works
Fragile X mental retardation protein: Nucleocytoplasmic shuttling and association with somatodendritic ribosomes.
Feng, Y., Gutekunst, C.-A., Eberhart, D. E., Yi, H., Warren, S. T., & Hersch, S. M. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-05-01539.1997 · Cited by 532 · see citing works
CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP
Mayford, M. R., Wang, J., Kandel, E. R., & O’Dell, T. J. (1995) · Cell · doi:10.1016/0092-8674(95)90009-8 · Cited by 525 · see citing works
FMRP Associates with Polyribosomes as an mRNP, and the I304N Mutation of Severe Fragile X Syndrome Abolishes This Association
Feng, Y., Absher, D., Eberhart, D. E., Brown, V., Malter, H. E., & Warren, S. T. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80012-x · Cited by 511 · see citing works
Locomotor Activity in D2 Dopamine Receptor-Deficient Mice Is Determined by Gene Dosage, Genetic Background, and Developmental Adaptations
Kelly, M. A., Rubinstein, M., Phillips, T. J., Lessov, C. N., Burkhart‐Kasch, S., Zhang, G., Bunzow, J. R., Fang, Y., Gerhardt, G. A., Grandy, D. K., et al. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03470.1998 · Cited by 447 · see citing works
Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome
Hinds, H. L., Ashley, C. T., Sutcliffe, J. S., Nelson, D. L., Warren, S. T., Housman, D. E., & Schalling, M. (1993) · Nature Genetics · doi:10.1038/ng0193-36 · Cited by 396 · see citing works
Self-citation
The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals
Eberhart, D. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.8.1083 · Cited by 390 · see citing works
Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F1 hybrids: implications of genetic background for single gene mutations and quantitative trait loci analyses
Owen, E. H., Logue, S. F., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00165-6 · Cited by 347 · see citing works
Self-citation
Stable hippocampal long-term potentiation elicited by ‘theta’ pattern stimulation
Staubli, U. V., & LYNCH, G. S. (1987) · Brain Research · doi:10.1016/0006-8993(87)91605-2 · Cited by 345 · see citing works
Characterization and localization of the FMR-1 gene product associated with fragile X syndrome
Verheij, C., Bakker, C. E., de Graaff, E., Keulemans, J., Willemsen, R., Verkerk, A. J. M. H., Galjaard, H., Reuser, A. J. J., Hoogeveen, A. T., & Oostra, B. A. (1993) · Nature · doi:10.1038/363722a0 · Cited by 343 · see citing works
Correlations between immediate early gene induction and the persistence of long-term potentiation
Abraham, W. C., Mason, S. E., Demmer, J., Williams, J. M., Richardson, C. L., Tate, W. P., Lawlor, P. A., & Dragunow, M. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90369-q · Cited by 303 · see citing works
Influence of actinomycin D, a RNA synthesis inhibitor, on long‐term potentiation in rat hippocampal neurons in vivo and in vitro.
Frey, U., Frey, S., Schollmeier, F., & Krug, M. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021179 · Cited by 273 · see citing works
DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning.
Paylor, R. E., Tracy, R., Wehner, J. M., & Rudy, J. W. (1994) · Behavioral Neuroscience · doi:10.1037//0735-7044.108.4.810 · Cited by 258 · see citing works
The fragile X mental retardation protein is associated with ribosomes
Khandjian, E. W., Corbin, F., Woerly, S., & Rousseau, F. (1996) · Nature Genetics · doi:10.1038/ng0196-91 · Cited by 251 · see citing works
A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci
Engler, P., Haasch, D. L., Pinkert, C. A., Doglio, L. T., Glymour, M. M., Brinster, R. L., & Storb, U. (1991) · Cell · doi:10.1016/0092-8674(91)90546-b · Cited by 217 · see citing works
Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain
Threadgill, D. W., Yee, D., Matin, A., Nadeau, J. H., & Magnuson, T. (1997) · Mammalian Genome · doi:10.1007/s003359900453 · Cited by 215 · see citing works
DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning.
Paylor, R. E., Tracy, R., Wehner, J. M., et al. (1994) · Behavioral Neuroscience · doi:10.1037/0735-7044.108.4.810 · Cited by 215 · see citing works
Mildly impaired water maze performance in maleFmr1 knockout mice
D'Hooge, R., Nagels, G., Franck, F., Bakker, C. E., Reyniers, E., Storm, K., Kooy, R. F., Oostra, B. A., Willems, P. J., & De Deyn, P. P. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00224-2 · Cited by 208 · see citing works
Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene
Kojima, N., Wang, J., Mansuy, I. M., Grant, S. G. N., Mayford, M. R., & Kandel, E. R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4761 · Cited by 188 · see citing works
A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture
Khandjian, E. W., Anny, F., Thibodeau, A., Tremblay, S., Côté, F., Devys, D., Mandel, J.-L., & Rousseau, F. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.5.783 · Cited by 141 · see citing works
Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene
LeCouter, J. E., Kablar, B., Hardy, W. R., Ying, C., Megeney, L. A., May, L. L., & Rudnicki, M. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.12.7455 · Cited by 141 · see citing works
Behavioral phenotype of fragile X syndrome: DSM‐III‐R autistic behavior in male children
Reiss, A. L., & Freund, L. S. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320430106 · Cited by 138 · see citing works
FMRP is associated to the ribosomes via RNA
Tamanini, F. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.6.809 · Cited by 137 · see citing works
Inhibition of protein synthesis in the dentate gyrus, but not the entorhinal cortex, blocks maintenance of long-term potentiation in rats
Otani, S., & Abraham, W. C. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90222-x · Cited by 95 · see citing works
Fragile X syndrome is less common than previously estimated
Morton, J. E., Bundey, S., Webb, T. P., MacDonald, F., Rindl, P. M., & Bullock, S. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.1.1 · Cited by 92 · see citing works
Association of FMRP with Ribosomal Precursor Particles in the Nucleolus
Willemsen, R., Bontekoe, C. J. M., Tamanini, F., GALJAARD, H., Hoogeveen, A. T., & Oostra, B. A. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1126 · Cited by 74 · see citing works
Tissue-specific expression of a FMR1/β-galactosidase fusion gene in transgenic mice
Hergersberg, M., Matsuo, K., Gassmann, M., Schaffner, W., Lüscher, B., Rülicke, T., & Aguzzi, A. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.3.359 · Cited by 71 · see citing works
Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: Transgenic rescue and interactions with gene background
McNamara, R. K., Stumpo, D. J., Morel, L. M., Lewis, M. H., Wakeland, E. K., Blackshear, P. J., & Lenox, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14517 · Cited by 67 · see citing works
Cognitive functioning and information processing of adult mentally retarded men with fragile‐X syndrome
Maes, B., Fryns, J. P., Walleghem, M. V., & BERGHE, H. V. D. (1994) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320500211 · Cited by 57 · see citing works
Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families
Cianchetti, C., Sannio‐Fancello, G., Fratta, A., Manconi, F., Orano, A., Pischedda, M. P., Pruna, D., Spinicci, G., Archidiacono, N., & Filippi, G. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320400222 · Cited by 41 · see citing works
Long‐term potentiation in the hippocampus of fragile X knockout mice
Godfraind, J., Reyniers, E., Boulle, K. D., D’Hooge, R., Deyn, P. P. D., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Willems, P. J. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960809)64:2 · Cited by 16 · see citing works
Induction of Gut Mucosal Immune Responses: Importance of Genetic Background and Th1/Th2 Cross‐Regulation
Kjerrulf, Grdic, Köpf, M., & Lycke (1998) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.1998.00316.x · Cited by 11 · see citing works
Untitled work
Turner (1996) · doi:10.1002/(sici)1096-8628(19960712)64:1

Flagged first, then by citations

Sorted by citations

Applications of the Morris water maze in the study of learning and memory
D’Hooge, R., & Deyn, P. P. D. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00067-4 · Cited by 2,035 · see citing works
The mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580 · see citing works
Self-citation
Trinucleotide Repeat Disorders
Orr, H. T., & Zoghbi, H. Y. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113042 · Cited by 1,365 · see citing works
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349 · see citing works
Molecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective
Santoro, M. R., Bray, S. M., & Warren, S. T. (2012) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132457 · Cited by 528 · see citing works
The Intense World Theory – A Unifying Theory of the Neurobiology of Autism
Markram, H., & Markram, H. (2010) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2010.00224 · Cited by 522 · see citing works
The use of behavioral test batteries: Effects of training history
McIlwain, K. L., Merriweather, M. Y., Yuva-Paylor, L. A., & Paylor, R. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00528-5 · Cited by 579 · see citing works
A Decade of Molecular Studies of Fragile X Syndrome
O'Donnell, W. T., & Warren, S. T. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142909 · Cited by 481 · see citing works
Biochemical mechanisms for translational regulation in synaptic plasticity
Klann, E., & Dever, T. E. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1557 · Cited by 422 · see citing works
Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome
Koekkoek, S. K. E., Yamaguchi, K., Milojkovic, B. A., Dortland, B. R., Ruigrok, T. J. H., Maex, R., Graaf, W. D., Smit, A. E., VanderWerf, F., Bakker, C. E., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.07.005 · Cited by 417 · see citing works
“For example, their enhanced startle responses to auditory stimuli and their reduced freezing behavior in response to both contextual and conditional fear stimuli indicate a malfunction of the amygdala (Chen and Toth, 2001; Nielsen et al., 2002; Paradee et al., 1999).”
Background
Understanding the molecular basis of fragile X syndrome
Jin, P. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.6.901 · Cited by 368 · see citing works
Deficits in trace fear memory and long-term potentiation in a mouse model for fragile X syndrome
Zhao, M.-G., Toyoda, H., Ko, S. W., Ding, H.-K., Wu, L.-J., & Zhuo, M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1520-05.2005 · Cited by 258 · see citing works
“, 2000), whereas others report deficits in both auditory and contextual fear conditioning (Paradee et al., 1999).”
Background
Metabotropic Receptor-Dependent Long-Term Depression Persists in the Absence of Protein Synthesis in the Mouse Model of Fragile X Syndrome
Nosyreva, E. D., & Huber, K. M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01316.2005 · Cited by 292 · see citing works
(Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features
Peier, A. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.8.1145 · Cited by 285 · see citing works
Fragile X mice develop sensory hyperreactivity to auditory stimuli
Chen, L., & Toth, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00036-7 · Cited by 345 · see citing works
Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome
Dölen, G., & Bear, M. F. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.150722 · Cited by 278 · see citing works
Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice
Holmes, A., Wrenn, C. C., Harris, A. P., Thayer, K. E., & Crawley, J. N. (2002) · Genes Brain & Behavior · doi:10.1046/j.1601-1848.2001.00005.x · Cited by 275 · see citing works
“…substrains, including 129/J and 129/SvJ (Crawley et al. 1997; Montkowski et al. 1997; Owen et al. 1997; Hengemihle et al. 1999) and shown that a 129 background strain can compromise the detection of a cognitive deficiency in mutant mice (Wolfer et al. 1997; Paradee et al. 1999; Dobkin et al. 2000).”
Background
Reduced Cortical Synaptic Plasticity and GluR1 Expression Associated with Fragile X Mental Retardation Protein Deficiency
Li, J., Pelletier, M. R., Perez-Velazquez, J. L., & Carlen, P. L. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.1085 · Cited by 268 · see citing works
Social approach in genetically engineered mouse lines relevant to autism
Moy, S. S., Nadler, J. J., Young, N. B., Nonneman, R. J., Grossman, A. W., Murphy, D. L., D’Ercole, A. J., Crawley, J. N., Magnuson, T. R., & Lauder, J. M. (2009) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2008.00452.x · Cited by 246 · see citing works
“For example, researchers have proposed that the C57BL/6J background confers resistance to effects of Fmr1 deficiency on spatial learning, while FVB/N-129/OlaHsd (FVB/129) leads to greater susceptibility (Dobkin et al. 2000, see also Paradee et al. 1999).”
Background
Fragile X mental retardation protein and synaptic plasticity
Sidorov, M. S., Auerbach, B. D., & Bear, M. F. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-15 · Cited by 243 · see citing works
“Interestingly, no difference has been found in the magnitude of L-LTP in the Fmr1 KO [61,62].”
BackgroundMethodInfluential
Social approach and repetitive behavior in eleven inbred mouse strains
Moy, S. S., Nadler, J. J., Young, N. B., Nonneman, R. J., Segall, S. K., Andrade, G. M., Crawley, J. N., & Magnuson, T. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.015 · Cited by 243 · see citing works
Modeling fragile X syndrome in the Fmr1 knockout mouse
Kazdoba, T. M., Leach, P. T., Silverman, J. L., & Crawley, J. N. (2014) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2014.01024 · Cited by 241 · see citing works
“In amydgaladependent delay-cued fear conditioning, a deficit was reported in Fmr1 KO mice (75,90), but other studies did not observe this effect (173-175).”
BackgroundResultInfluential
Brain-Derived Neurotrophic Factor Rescues Synaptic Plasticity in a Mouse Model of Fragile X Syndrome
Lauterborn, J. C., Rex, C. S., Kramár, E. A., Chen, L. Y., Pandyarajan, V., LYNCH, G. S., & Gall, C. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2624-07.2007 · Cited by 241 · see citing works
“, 2005) cortices of Fmr1-KO mice, there is no evidence for an impairment in the hippocampus (Godfraind et al., 1996; Paradee et al., 1999; Li et al., 2002; Larson et al., 2005).”
Vesicular Glutamate Transporter VGLUT2 Expression Levels Control Quantal Size and Neuropathic Pain
Moechars, D., Weston, M. C., Leo, S., Callaerts‐Vegh, Z., Goris, I., Daneels, G., Buist, A., Cik, M., van der Spek, P. J., Kass, S. U., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2556-06.2006 · Cited by 226 · see citing works
“Cue- and context-dependent fear conditioning were tested in a previously described protocol (Paradee et al., 1999).”
Method
Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic‐like responses
Spencer, C. M., Alekseyenko, O. V., Hamilton, S. M., Thomas, A. M., Serysheva, E., Yuva‐Paylor, L. A., & Paylor, R. E. (2011) · Autism Research · doi:10.1002/aur.168 · Cited by 215 · see citing works
Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse
Mineur, Y. S., Sluyter, F., de Wit, S., Oostra, B. A., & Crusio, W. E. (2002) · Hippocampus · doi:10.1002/hipo.10005 · Cited by 216 · see citing works
“…quantitatively abnormal dendritic spining in the pyramidal cells of the occipital cortex (Comery et al., 1997), they do not differ in shortterm potentiation (STP), LTP, or late-phase protein synthesisdependent hippocampal LTP in comparison to controls (Godfraind et al., 1996; Paradee et al., 1999).”
Result
The State of Synapses in Fragile X Syndrome
Pfeiffer, B. E., & Huber, K. M. (2009) · The Neuroscientist · doi:10.1177/1073858409333075 · Cited by 214 · see citing works
A phenotypic and molecular characterization of the fmr1‐tm1Cgr Fragile X mouse
Yan, Q. J., Asafo‐Adjei, P. K., Arnold, H. M., Brown, R. E., & Bauchwitz, R. P. (2004) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2004.00087.x · Cited by 213 · see citing works
“fmr1-tm1Cgr hippocampal long-term potentiation (LTP) have been found (Godfraind et al. 1996; Paradee et al. 1999; Valentine et al. 2000), a deficit in cortical LTP has been described (Li et al.”
Background
mGluR5 Positive Allosteric Modulators Facilitate both Hippocampal LTP and LTD and Enhance Spatial Learning
Ayala, J. E., Chen, Y., Banko, J. L., Sheffler, D. J., Williams, R. D., Telk, A. N., Watson, N. L., Xiang, Z., Zhang, Y., Jones, P. J., et al. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.30 · Cited by 206 · see citing works
“…with Fragile X Syndrome (FXS) selectively increase mGluR5-mediated hippocampal LTD (Huber et al., 2002; Bear et al., 2004; Nosyreva and Huber, 2006), while having no effect (Godfraind et al., 1996; Paradee et al., 1999; Li et al., 2002) or depressing hippocampal LTP (Lauterborn et al., 2007).”
New insights into fragile X syndrome: from molecules to neurobehaviors
Jin, P., & Warren, S. T. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00033-1 · Cited by 203 · see citing works
Ionotropic Glutamate Receptors & CNS Disorders
Bowie, D. (2008) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152708784083821 · Cited by 200 · see citing works
Advances in behavioral genetics: mouse models of autism
Moy, S. S., & Nadler, J. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002082 · Cited by 197 · see citing works
Circuit and Plasticity Defects in the Developing Somatosensory Cortex ofFmr1Knock-Out Mice
Bureau, I., Shepherd, G. M. G., & Svoboda, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1076-08.2008 · Cited by 201 · see citing works
“Fmr1 ko mice have learning deficits (Dutch–Belgian Fragile X Consortium, 1994; Paradee et al., 1999; Peier et al., 2000), abnormal social behaviors (Spencer et al., 2005; Mineur et al., 2006), and audiogenic seizures (Musumeci et al., 2000; Chen and Toth, 2001; Yan et al., 2004).”
Background
Maternal behavior deficits in nulliparous oxytocin knockout mice
Pedersen, C. A., Vadlamudi, S. V., Boccia, M. L., & Amico, J. A. (2006) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00162.x · Cited by 190 · see citing works
“The behavioral phenotypes resulting from the inactivation of some other genes have varied depending upon the background strain (Dobkin et al. 2000; Paradee et al. 1999; Toth 2003).”
Background
Dendritic pathology in mental retardation: from molecular genetics to neurobiology
Dierssen, M., & Ramakers, G. J. A. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00224.x · Cited by 190 · see citing works
“Loss of FMRP in mice did not affect LTP in hippocampal area CA1, but LTP in cerebral cortex was impaired and associated with a decrease in the GluRI subunit (Godfraind et al. 1996; Li et al. 2002; Paradee et al. 1999).”
Background
Role of HuD and other RNA‐binding proteins in neural development and plasticity
Perrone‐Bizzozero, N. I., & Bolognani, F. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10175 · Cited by 186 · see citing works
“One explanation could be the genetic background of the knock out (KO) mice, but more work on this area is needed (DutchBelgian Fragile X Consortium, 1994; D’Hooge et al., 1997; Fisch et al., 1999; Paradee et al., 1999; Dobkin et al., 2000).”
Background
Behavioral phenotypes of genetic mouse models of autism
Kazdoba, T. M., Leach, P. T., & Crawley, J. N. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12256 · Cited by 179 · see citing works
“…characterize FXS. Deficits have been observed in contextual, cued and trace fear conditioning and/or context discrimination in Genes, Brain and Behavior (2016) 15: 7–26 17 Fmr1 KO mice on B6 and sighted FVB backgrounds (Auerbach et al. 2011; Ding et al. 2014; Paradee et al. 1999; Zhao et al. 2005).”
BackgroundResultInfluential
Fragile X Syndrome: The GABAergic System and Circuit Dysfunction
Paluszkiewicz, S. M., Martin, B. S., & Huntsman, M. M. (2011) · Developmental Neuroscience · doi:10.1159/000329420 · Cited by 177 · see citing works
“…evidence of amygdala dysfunction in FXS patients and mouse models alike [Budimirovic et al., 2006; Hagerman et al., 2009; McNaughton et al., 2008; Paradee et al., 1999], the basolateral amygdala of Fmr1 KO mice is characterized by broad and severe inhibitory defects, including reductions in the…”
Dendritic spine dysgenesis in autism related disorders
Phillips, M. L., & Pozzo‐Miller, L. D. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.011 · Cited by 176 · see citing works
Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice
Pietropaolo, S., Guilleminot, A., Martin, B., D'Amato, F. R., & Crusio, W. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017073 · Cited by 178 · see citing works
Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome.
McNaughton, C. H., Moon, J., Strawderman, M. S., Maclean, K. N., Evans, J., & Strupp, B. J. (2008) · Behavioral Neuroscience · doi:10.1037/0735-7044.122.2.293 · Cited by 174 · see citing works
“…Brown, & Bauchwitz, 2004) or have revealed very small deficits in the Fmr1 KO mice that are apparent only in some background strains (Bakker et al., 1994; Dobkin et al., 2000; Paradee et al., 1999) Results seemingly contradictory with the phenotype of humans with FXS have also been reported.”
Background
Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics
Kazdoba, T. M., Leach, P. T., Yang, M., Silverman, J. L., Solomon, M., & Crawley, J. N. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_5003 · Cited by 172 · see citing works
“Water maze and fear conditioning deficits were reported in mice with mutations in Pten, Tsc1, Shank3, Cntnap2, En2, and in the BTBR inbred strain, among others (Upchurch and Wehner 1988; The Dutch-Belgian Fragile et al. 1994; D’Hooge et al. 1997; Paradee et al. 1999; Goorden et al. 2007; Moy et al. 2007; MacPherson et…”
Background
Ras Signaling Mechanisms Underlying Impaired GluR1-Dependent Plasticity Associated with Fragile X Syndrome
Hu, H., Qin, Y., Bochorishvili, G., Zhu, Y., Aelst, L. V., & Zhu, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1496-08.2008 · Cited by 165 · see citing works
“…of FMR1 knock-out mice has been extensively examined, but whether learning is impaired in these mice remains unclear (The Dutch-Belgian Fragile X Consortium, 1994; D’Hooge et al., 1997; Paradee et al., 1999; Dobkin et al., 2000; Van Dam et al., 2000; Frankland et al., 2004; Zhao et al., 2005).”
BackgroundMethodResultInfluential
Cognitive Dysfunctions in Intellectual Disabilities: The Contributions of the Ras-MAPK and PI3K-AKT-mTOR Pathways
Borrie, S. C., Brems, H., Legius, E., & Bagni, C. (2017) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091416-035332 · Cited by 167 · see citing works
The neuroanatomy and neuroendocrinology of fragile X syndrome
Hessl, D., Rivera, S. M., & Reiss, A. L. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20004 · Cited by 165 · see citing works
“Paradee and colleagues [Paradee et al., 1999] demonstrated an abnormal conditioned fear response (less freezing behavior during contextual and cued conditions) in the knockout mouse compared to controls.”
Background
Dendritic spine abnormalities in the occipital cortex of C57BL/6Fmr1 knockout mice
McKinney, B. C., Grossman, A. W., Elisseou, N. M., & Greenough, W. T. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30183 · Cited by 184 · see citing works
“Mouse background has been demonstrated previously to affect other aspects of Fmr1 KO phenotype [e.g., Paradee et al., 1999; Dobkin et al., 2000].”
Background
Ras and Rap Signaling in Synaptic Plasticity and Mental Disorders
Stornetta, R. L., & Zhu, J. (2010) · The Neuroscientist · doi:10.1177/1073858410365562 · Cited by 159 · see citing works
Fmr1 knockout mouse has a distinctive strain-specific learning impairment
Dobkin, C., Rabe, A., Dumas, R., El Idrissi, A., Haubenstock, H., & Ted Brown, W. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00292-x · Cited by 179 · see citing works
Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice
Dam, D. V., D’Hooge, R., Hauben, E., Reyniers, E., Gantois, I., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Deyn, P. P. D. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00296-5 · Cited by 145 · see citing works
“[23] were able to replicate only part of these results, which could have been due to strain differences between C57BL/6 and 129Re/J influencing the Fmr1 knockout phenotype.”
BackgroundResultInfluential
Defective Neuronal Development in the Mushroom Bodies of Drosophila Fragile X Mental Retardation 1 Mutants
Michel, C. I., Kraft, R., & Restifo, L. L. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1102-04.2004 · Cited by 145 · see citing works
“Another important clue is provided by genetic background effects on behavioral (Paradee et al., 1999; Dobkin et al., 2000) and neuroanatomical (Ivanco and Greenough, 2002; Mineur et al.”
Background
Behavioral deficits in an Angelman syndrome model: Effects of genetic background and age
Huang, H., Burns, A. J., Nonneman, R. J., Baker, L. K., Riddick, N. V., Nikolova, V. D., Riday, T. T., Yashiro, K., Philpot, B. D., & Moy, S. S. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.12.052 · Cited by 141 · see citing works
Early developmental alterations in GABAergic protein expression in fragile X knockout mice
Adusei, D. C., Pacey, L. K. K., Chen, D., & Hampson, D. R. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.05.002 · Cited by 139 · see citing works
“LTP in the hippocampus did not find a difference in early- or late-phase LTP between wild-type and Fmr1 knockout mice (Godfraind et al., 1996; Paradee et al., 1999).”
Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome
Suvrathan, A., Hoeffer, C. A., Wong, H., Klann, E., & Chattarji, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002262107 · Cited by 137 · see citing works
“The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala (2, 13, 17).”
Background
Glutamatergic synapses in neurodevelopmental disorders
Moretto, E., Murru, L., Martano, G., Sassone, J., & Passafaro, M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.09.014 · Cited by 136 · see citing works
“However, the prominent forms of plasticity, the NMDAR-dependent LTP and LTD, were found unaltered in these animals (Godfraind et al., 1996; Huber et al., 2002; Paradee et al., 1999).”
Background
Mouse models of autism spectrum disorders: The challenge for behavioral genetics
Moy, S. S., Nadler, J. J., Magnuson, T., & Crawley, J. N. (2006) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30081 · Cited by 135 · see citing works
Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein
Larson, J., Jessen, R. E., Kim, D., Fine, A.-K. S., & du Hoffmann, J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2638-05.2005 · Cited by 135 · see citing works
“However, excitatory synapses in field CA1 of hippocampus of Fmr1 KO mice were found to exhibit normal long-term potentiation (LTP), a learning-related form of synaptic plasticity involving spine shape changes (Godfraind et al., 1996; Paradee et al., 1999).”
Background
Of mice and the fragile X syndrome
Kooy, R. F. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00017-9 · Cited by 134 · see citing works
Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes
Bardoni, B., & Mandel, J. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00300-3 · Cited by 129 · see citing works
The GABAA Receptor Agonist THIP Ameliorates Specific Behavioral Deficits in the Mouse Model of Fragile X Syndrome
Olmos-Serrano, J. L., Corbin, J. G., & Burns, M. P. (2011) · Developmental Neuroscience · doi:10.1159/000332884 · Cited by 128 · see citing works
Altered Hippocampal Synaptic Plasticity in the Fmr1 Gene Family Knockout Mouse Models
Zhang, J., Hou, L., Klann, E., & Nelson, D. L. (2009) · Journal of Neurophysiology · doi:10.1152/jn.90558.2008 · Cited by 126 · see citing works
Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity
Franchini, L., Carrano, N., Luca, M. D., & Gardoni, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041538 · Cited by 124 · see citing works
Mechanism-based approaches to treating fragile X
Dölen, G., Carpenter, R. L., Ocain, T. D., & Bear, M. F. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.02.008 · Cited by 124 · see citing works
“…plasticity can be triggered experimentally, producing longtermpotentiation (LTP) and long-termdepression (LTD) of the synapse, using a variety of inductionprotocols, including: theta-burst stimulation (TBS), high-frequency stimulation (HFS), low-frequency stimulation (LFS), paired-pulse LFS…”
BackgroundResultInfluential
Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background
Ding, Q., Sethna, F., & Wang, H. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.05.046 · Cited by 121 · see citing works
Neuropsychiatric Symptoms of Fragile X Syndrome
Tsiouris, J. A., & Brown, W. T. (2004) · CNS Drugs · doi:10.2165/00023210-200418110-00001 · Cited by 122 · see citing works
Of Men and Mice: Modeling the Fragile X Syndrome
Dahlhaus, R. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00041 · Cited by 118 · see citing works
“, 2015), thereby contrasting not only the majority of data obtained from Fmr1−/y mice (D’Hooge et al., 1997; Paradee et al., 1999; Van Dam et al., 2000; Baker et al., 2010, reviewed in Kazdoba et al., 2014), but also the weak performance of FXS patients in tasks requiring the solution of new problems (Dykens et al.”
BackgroundMethodResultInfluential
Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice
Wilson, B. M., & Cox, C. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610875104 · Cited by 121 · see citing works
Knockout mouse model for Fxr2: a model for mental retardation
Bontekoe, C. J. M. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.487 · Cited by 120 · see citing works
Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins
Spencer, C. M., Serysheva, E., Yuva‐Paylor, L. A., Oostra, B. A., Nelson, D. L., & Paylor, R. E. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl121 · Cited by 115 · see citing works
“Indeed, studies have reported differences in cognitive response based on strain background ( 40 ,41).”
Background
Early Postnatal Plasticity in Neocortex of Fmr1 Knockout Mice
Desai, N. S., Casimiro, T. M., Gruber, S. M., & Vanderklish, P. W. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00221.2006 · Cited by 92 · see citing works
Glycogen Synthase Kinase-3 Inhibitors Reverse Deficits in Long-term Potentiation and Cognition in Fragile X Mice
Franklin, A. V., King, M. K., Palomo, V., Martı́nez, A., McMahon, L. L., & Jope, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.003 · Cited by 109 · see citing works
Anatomical phenotyping in a mouse model of fragile X syndrome with magnetic resonance imaging
Ellegood, J., Pacey, L. K. K., Hampson, D. R., Lerch, J. P., & Henkelman, R. M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.03.038 · Cited by 110 · see citing works
“Some of the other known phenotypes of FX KO mice, such as the learning deficits, are also subtle and are often dependent on the background strain of the mice (Dobkin et al., 2000; Paradee et al., 1999).”
Background
Conserved Hippocampal Cellular Pathophysiology but Distinct Behavioural Deficits in a New Rat Model of FXS
Till, S. M., Asiminas, A., Jackson, A. D., Katsanevaki, D., Barnes, S. A., Osterweil, E. K., Bear, M. F., Chattarji, S., Wood, E. R., Wyllie, D. J. A., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv299 · Cited by 109 · see citing works
Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back
Gross, C., Hoffmann, A., Bassell, G. J., & Berry-Kravis, E. M. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0355-9 · Cited by 105 · see citing works
“Initial analyses to assess defects in hippocampal dependent learning and memory using classic Morris water maze assays revealed only subtle and varying defects in Fmr1 mice [213].”
Method
Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond
Groß, C., Berry‐Kravis, E., & Bassell, G. J. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.137 · Cited by 103 · see citing works
“Initial studies using ‘classic’ hippocampus-dependent learning tasks, such as Morris Water Maze and fear conditioning, revealed no or very subtle defects in the Fmr1 KO mice (The Dutch-Belgian Fragile et al, 1994; Paradee et al, 1999; Van Dam et al, 2000).”
BackgroundResult
Fragile X Syndrome and Targeted Treatment Trials
Hagerman, R. J., Lauterborn, J. C., Au, J., & Berry‐Kravis, E. (2011) · Results and problems in cell differentiation · doi:10.1007/978-3-642-21649-7_17 · Cited by 104 · see citing works
“…Morris water maze (Bakker and Consortium 1994; D’Hooge et al. 1997; Dobkin et al. 2000), radial maze (Mineur et al. 2002), fear conditioning (Paradee et al. 1999; Qin et al. 2005), object discrimination (Ventura et al. 2004), odor discrimination (Larson et al. 2008), and eye blink…”
Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia
Crabtree, G. W., & Gogos, J. A. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00028 · Cited by 102 · see citing works
Male and female Fmr1 knockout mice on C57 albino background exhibit spatial learning and memory impairments
Baker, K. B., Wray, S. P., Ritter, R., Mason, S. M., Lanthorn, T. H., & Savelieva, K. V. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00585.x · Cited by 101 · see citing works
“Another study, using mice congenic on a C57Bl/6J background, did not find any impairments in Fmr1 KO mice in the MWM, including reversal learning (Paradee et al. 1999).”
BackgroundMethodInfluential
Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders
Francis, S. M., Sagar, A., Levin-Decanini, T., Liu, W., Carter, C. S., & Jacob, S. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.021 · Cited by 101 · see citing works
“By most accounts Fmr1 KO mice appear to have relatively normal behavior, but research has shown that the behavioral and cognitive deficits of the KO are actually quite subtle and parallel FXS patients (Berry-Kravis et al., 2002; D’Hooge et al., 1997; Paradee et al., 1999; Peier et al., 2000).”
Background
Deregulated mTOR-mediated translation in intellectual disability.
Troca-Marín, J. A., Alves-Sampaio, A., & Montesinos, M. (2012) · Progress in neurobiology · doi:10.1016/j.pneurobio.2012.01.005 · Cited by 97 · see citing works
Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice
Aloisi, E., Corf, K. L., Dupuis, J. P., Zhang, P., Ginger, M. R., Labrousse, V. F., Spatuzza, M., Haberl, M. G., Costa, L., Shigemoto, R., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01191-2 · Cited by 98 · see citing works
Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission
der Jeugd, A. V., Ahmed, T., Burnouf, S., Bélarbi, K., Hamdame, M., Grosjean, M., Humez, S., Balschun, D., Blum, D. L., Buée, L., et al. (2010) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2010.12.005 · Cited by 98 · see citing works
“The contextual fear conditioning experiment was based on the protocol used by Paradee et al. (1999).”
Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development
Pop, A. S., Gomez‐Mancilla, B., Neri, G., Willemsen, R., & Gasparini, F. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3330-3 · Cited by 94 · see citing works
“…in results obtained with the Morris water maze, where some studies found impairment in the reversal trials in Fmr1 KO mice (Bakker et al. 1994; D’Hooge et al. 1997), while others have not observed any difference between KO and wild-type mice in learning and reversal tasks (Paradee et al. 1999).”
BackgroundResult
Autism Spectrum Disorders: Translating human deficits into mouse behavior
Pasciuto, E., Borrie, S. C., Kanellopoulos, A. K., Santos, A. R. S., Cappuyns, E., D’Andrea, L., Pacini, L., & Bagni, C. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.07.013 · Cited by 92 · see citing works
Fmr1 knockout mice show reduced anxiety and alterations in neurogenesis that are specific to the ventral dentate gyrus
Eadie, B. D., Zhang, W. N., Boehme, F., Gil‐Mohapel, J., Kainer, L., Simpson, J. M., & Christie, B. R. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.08.001 · Cited by 94 · see citing works
Haploinsufficiency of Cyfip1 Produces Fragile X-Like Phenotypes in Mice
Bozdagi, O., Sakurai, T., Dorr, N., Pilorge, M., Takahashi, N., & Buxbaum, J. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042422 · Cited by 97 · see citing works
“LTP in CA1 induced by high frequency stimulation is also known to be unaffected in Fmr1 knockout mice [36,37], however, LTP elicited by threshold theta burst afferent stimulation is impaired in young adult Fmr1 knockout mice [38] which is reversed by BDNF perfusion.”
Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation
Qin, M., Kang, J. Y., & Smith, C. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242377399 · Cited by 93 · see citing works
Genes, plasticity and mental retardation
Vaillend, C., Poirier, R., & Laroche, S. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.01.009 · Cited by 91 · see citing works
“ARHGEF6/ -PIX XLMR siRNA-knock-down Abnormal spine morphogenesis [134] Ube3a/E6-AP Angelman m−/p+ LTP↘ (CA1) Abnormal spine morphology [42,92,168] FMR1/FMRP Fragile-X KO CA1: mGluR-LTD↗, TBS-LTP↘, normal HFS-induced E-LTP, L-LTP; cortex/amygdala: LTP↘, normal PTP, PPF Abnormal dendritic branching and spine morphology,…”
Background
Complications associated with genetic background effects in models of experimental epilepsy
Schauwecker, P. E. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)35014-3 · Cited by 92 · see citing works
The 5-HT 1A receptor knockout mouse and anxiety
Olivier, B., Pattij, T., Wood, S. J., Oosting, R. S., Sarnyai, Z., & Tóth, M. (2001) · Behavioural Pharmacology · doi:10.1097/00008877-200111000-00004 · Cited by 89 · see citing works
Reduction of BDNF expression in Fmr1 knockout mice worsens cognitive deficits but improves hyperactivity and sensorimotor deficits
Uutela, M., Lindholm, J., Louhivuori, V., Wei, H., Louhivuori, L. M., Pertovaara, A., Åkerman, K. E. O., Ċastrén, E., & Castrén, M. L. (2012) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2012.00784.x · Cited by 88 · see citing works
“…KO mice in the MWM has yielded conflicting results which may be explained by genetic and environmental factors and different behavioral testing strategies (Bakker et al. 1994; Dı́ Hooge et al. 1997; Dobkin et al. 2000; Gantois et al. 2001; Kooy et al. 1996; Paradee et al. 1999; Peier et al. 2000).”
Background
Metabotropic Glutamate Receptors as Therapeutic Targets for Schizophrenia
Vinson, P., & Conn, P. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.005 · Cited by 95 · see citing works
“…and LTD and that a disruption of this balance may be characteristic of cognitionimpairing pathologies such as observed in models of Fragile X (Bear et al., 2004; Godfraind et al., 1996; Huber et al., 2002; Lauterborn et al., 2007; Li et al., 2002; Nosyreva and Huber, 2006; Paradee et al., 1999).”
Background
Attentional dysfunction, impulsivity, and resistance to change in a mouse model of fragile X syndrome.
Moon, J., Beaudin, A. E., Verosky, S. C., Driscoll, L. L., Weiskopf, M., Levitsky, D. A., Crnic, L. S., & Strupp, B. J. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.6.1367 · Cited by 88 · see citing works
“…maze performance, Fmr1 KO mice have been found to perform less well than controls specifically when the location of the platform has been moved (reversal trials), a pattern that may implicate impairments in arousal regulation and/or inhibitory control (D'Hooge et al., 1997; Paradee et al., 1999).”
BackgroundMethodResultInfluential
Understanding fragile X syndrome: insights from animal models
Bakker, C. E., & Oostra, B. A. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072845 · Cited by 87 · see citing works
“In addition, tests measuring exploration, hyperactivity, anxiety, conditioned fear and aggression were performed (Bakker et al., 1994; Kooy et al., 1996; D’Hooge et al., 1997; Paradee et al., 1999; Dobkin et al., 2000; Peier et al., 2000; Van Dam et al., 2000; Mineur et al., 2002).”
BackgroundMethodInfluential
Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach usPreprint
Santos, A. R., Kanellopoulos, A. K., & Bagni, C. (2014) · Learning & Memory · doi:10.1101/lm.035956.114 · Cited by 86 · see citing works
“…absence of FMRP. Memory consolidation and retrieval are not affected either; both Fmr1 KO and WT mice spent more time in the target quadrant (Kooy et al. 1996; Paradee et al. 1999; Yan et al. 2004), indicating that both groups learned and remembered the initial position of the escape plat- form.”
BackgroundMethodResultInfluential
Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon
Eagleson, K. L., Schlueter, L. J., Ahrens, E. T., Mills, P. H., Does, M. D., Nickols, J., & Levitt, P. R. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.06.012 · Cited by 83 · see citing works
“…upon genetic background, as are the neural phenotypes produced by mutations of p75NGF (Greferath et al., 2000), Unc5c (Burgess et al., 2006), fmr-1 (Paradee et al., 1999,Dobkin et al., 2000,Ivanco and Greenough, 2002,Mineur et al., 2002,Errijgers and Kooy, 2004) and Pax2 (Schwarz et al., 1997).”
Background
Brief Report: Visual Processing of Faces in Individuals with Fragile X Syndrome: An Eye Tracking Study
Farzin, F., Rivera, S. M., & Hessl, D. R. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-009-0744-1 · Cited by 83 · see citing works
“…of cortisol, by means of a cascade of hormones along the hypothalamic-pituitary-adrenal (HPA) axis, involves feedback between several limbic structures, among which the amygdala plays a significant role, and which have been implicated in FXS (Binstock 1995; Hessl et al. 2004; Paradee et al. 1999).”
Effects of chronic immobilization stress on anxiety-like behavior and basolateral amygdala morphology in Fmr1 knockout mice
Qin, M., Xia, Z., Huang, T., & Smith, C. B. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.047 · Cited by 83 · see citing works
“…significant enotypes under either US or CS conditions (*** P 0.001) and betwe behavior (Spencer et al., 2008; McNaughton et al., 2008; Mineur et al., 2006; Liu and Smith, 2009) and decreased freezing responses to both contextual and cued conditioning (Paradee et al., 1999; Zhao et al., 2005).”
BackgroundInfluential
Hippocampal dysfunction and cognitive impairment in Fragile-X Syndrome
Bostrom, C. A., Yau, S., Majaess, N. M., Vetrici, M. A., Gil‐Mohapel, J., & Christie, B. R. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.033 · Cited by 79 · see citing works
“However, since contextual fear is also dependent on proper amygdala functioning, the interpretation of these findings in the context of Fmr1 KO hippocampal function may not be straightforward (Paradee et al., 1999).”
BackgroundMethodInfluential
Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats
Tian, Y., Yang, C., Shang, S., Cai, Y., Deng, X., Zhang, J., Shao, F., Zhu, D., Liu, Y., Chen, G., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00269 · Cited by 82 · see citing works
“…revealed normal trial performance, whereas mixed results have been reported with respect to the memory acquisition and reversal learning processes (The Dutch-Belgian Fragile X Consortium, 1994; Kooy et al., 1996; D’Hooge et al., 1997; Paradee et al., 1999; Baker et al., 2010; Uutela et al., 2012).”
Result
Naturalness and Animal Welfare
Yeates, J. W. (2018) · Animals · doi:10.3390/ani8040053 · Cited by 80 · see citing works

Long‐term potentiation in the hippocampus of fragile X knockout mice
Godfraind, J., Reyniers, E., Boulle, K. D., D’Hooge, R., Deyn, P. P. D., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Willems, P. J. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960809)64:2 · Cited by 16 · see citing works
Role of hippocampal NMDA receptors in a mouse model for fragile x mental retardation syndrome
Mittmann, T. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.168633 · Cited by 2 · see citing works
Fmr1 knockout mouse has a distinctive strain-specific learning impairment
Dobkin, C., Rabe, A., Dumas, R., El Idrissi, A., Haubenstock, H., & Ted Brown, W. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00292-x · Cited by 179 · see citing works
Mildly impaired water maze performance in maleFmr1 knockout mice
D'Hooge, R., Nagels, G., Franck, F., Bakker, C. E., Reyniers, E., Storm, K., Kooy, R. F., Oostra, B. A., Willems, P. J., & De Deyn, P. P. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00224-2 · Cited by 208 · see citing works
Of mice and the fragile X syndrome
Kooy, R. F. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00017-9 · Cited by 134 · see citing works

Authors: Paradee, W., Melikian, H. E., Rasmussen, D. L., Kenneson, A., Conn, P. J., & Warren, S. T.
Affiliations: Howard Hughes Medical Institute (US)
Emory University (US)
Corresponding author: Warren, S.T.
ORCID: Paradee, W.
Melikian, H.E.
Kenneson, A.
Conn, P.J.
Warren, S.T.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 1999-09
Volume: 94
Issue: 1
Pages: 185-192
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/s0306-4522(99)00285-7
OpenAlex: W2110871941
Cited by: 305
References: 51
Citations by year: 2026: 2 · 2025: 1 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 15 · 2018: 11 · 2017: 17 · 2016: 5 · 2015: 14 · 2014: 19 · 2013: 16 · 2012: 15
FWCI: 4.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37 HD20521, P01 HD35576, R37HD020521, P01HD035576)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: fragile X syndrome, Fmr1 knockout mice, FMRP, amygdala, contextual fear, spatial learning, hippocampal long-term potentiation, strain differences, C57BL/6 mice, 129 mice, freezing behavior, translational regulation
MeSH terms: Amygdala, Animals, Conditioning, Psychological, Electrophysiology, Fear, Female, Fragile X Syndrome, Genotype, Hippocampus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Phenotype, Spatial Behavior, RNA-Binding Proteins, Long-Term Potentiation, Mice, Knockout, Maze Learning, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks