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Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function
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.
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“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
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Cites
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
Self-citationDifferential 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
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
Synaptic tagging and long-term potentiation
Frey, U., & Morris, R. G. M. (1997) · Nature · doi:10.1038/385533a0 · Cited by 1,736
LeDoux, J. E. (1995) · Annual Review of Psychology · doi:10.1146/annurev.ps.46.020195.001233 · Cited by 1,646
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
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
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
Short-Term Synaptic Plasticity
Zucker, R. S. (1989) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.12.030189.000305 · Cited by 1,450
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
Research works printed but not linked: 4
- Hagerman R. (1998) Clinical and diagnostic aspects of fragile X syndrome. In Genetic Instabilities and Hereditary Neurological Diseases (eds Wells R. D. and Warren S. T.), pp. 15–25. Academic, San Diego.
- Imbert G., Feng Y., Nelson D. L., Warren S. T. and Mandel J.-L. (1998) FMR1 and mutations in fragile X syndrome: molecular biology, biochemistry and genetics. In Genetic Instabilities and Hereditary Neurological Diseases (eds Wells R. D. and Warren S. T.), pp. 27–53. Academic, San Diego.
- Kooy, 1996, Transgenic mouse model for the fragile X syndrome, Am. J. Med. Genet., 64, 241, 10.1002/(SICI)1096-8628(19960809)64:2<241::AID-AJMG1>3.0.CO;2-X · DOI
- Oostra B. A. and Willems P. J. (1998) Murine model of fragile X syndrome. In Genetic Instabilities and Hereditary Neurological Diseases (eds Wells R. D. and Warren S. T.), pp. 55–62. Academic, San Diego.
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Markram, H., & Markram, H. (2010) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2010.00224 · Cited by 571
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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
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 487
Biochemical mechanisms for translational regulation in synaptic plasticity
Klann, E., & Dever, T. E. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1557 · Cited by 433
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 412
“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).”
BackgroundUnderstanding the molecular basis of fragile X syndrome
Jin, P. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.6.901 · Cited by 369
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 296
“, 2000), whereas others report deficits in both auditory and contextual fear conditioning (Paradee et al., 1999).”
BackgroundNosyreva, E. D., & Huber, K. M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01316.2005 · Cited by 301
(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
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
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
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 284
“…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).”
BackgroundLi, J., Pelletier, M. R., Perez-Velazquez, J. L., & Carlen, P. L. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.1085 · Cited by 275
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
“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).”
BackgroundFragile 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 255
“Interestingly, no difference has been found in the magnitude of L-LTP in the Fmr1 KO [61,62].”
BackgroundMethodInfluentialSocial 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 240
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
“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).”
BackgroundResultInfluentialBrain-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 244
“, 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
“Cue- and context-dependent fear conditioning were tested in a previously described protocol (Paradee et al., 1999).”
MethodSpencer, 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 225
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
“…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).”
ResultThe State of Synapses in Fragile X Syndrome
Pfeiffer, B. E., & Huber, K. M. (2009) · The Neuroscientist · doi:10.1177/1073858409333075 · Cited by 216
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
“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.”
BackgroundAyala, 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
“…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
Ionotropic Glutamate Receptors & CNS Disorders
Bowie, D. (2008) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152708784083821 · Cited by 207
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 204
Circuit and Plasticity Defects in the Developing Somatosensory Cortex of Fmr1 Knock-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
“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).”
BackgroundMaternal 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
“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).”
BackgroundDendritic 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 191
“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).”
BackgroundRole 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
“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).”
BackgroundBehavioral 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 187
“…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).”
BackgroundResultInfluentialFragile 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 185
“…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 188
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
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
“…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.”
BackgroundTranslational 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 185
“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…”
BackgroundHu, 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 168
“…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).”
BackgroundMethodResultInfluentialBorrie, 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 169
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
“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.”
BackgroundDendritic 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
“Mouse background has been demonstrated previously to affect other aspects of Fmr1 KO phenotype [e.g., Paradee et al., 1999; Dobkin et al., 2000].”
BackgroundRas and Rap Signaling in Synaptic Plasticity and Mental Disorders
Stornetta, R. L., & Zhu, J. (2010) · The Neuroscientist · doi:10.1177/1073858410365562 · Cited by 161
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
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
“[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.”
BackgroundResultInfluentialMichel, C. I., Kraft, R., & Restifo, L. L. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1102-04.2004 · Cited by 145
“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.”
BackgroundBehavioral 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
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
“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).”
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
“The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala (2, 13, 17).”
BackgroundGlutamatergic 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 146
“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).”
BackgroundMouse 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 141
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
“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).”
BackgroundOf mice and the fragile X syndrome
Kooy, R. F. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00017-9 · Cited by 138
Bardoni, B., & Mandel, J. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00300-3 · Cited by 129
Olmos-Serrano, J. L., Corbin, J. G., & Burns, M. P. (2011) · Developmental Neuroscience · doi:10.1159/000332884 · Cited by 134
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
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 127
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 129
“…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…”
BackgroundResultInfluentialBehavioral 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 131
Neuropsychiatric Symptoms of Fragile X Syndrome
Tsiouris, J. A., & Brown, W. T. (2004) · CNS Drugs · doi:10.2165/00023210-200418110-00001 · Cited by 120
Of Men and Mice: Modeling the Fragile X Syndrome
Dahlhaus, R. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00041 · Cited by 133
“, 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.”
BackgroundMethodResultInfluentialAbsence 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
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
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 123
“Indeed, studies have reported differences in cognitive response based on strain background ( 40 ,41).”
BackgroundEarly 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 113
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 113
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
“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).”
BackgroundTill, 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
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
“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].”
MethodTherapeutic 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 109
“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).”
BackgroundResultFragile 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 111
“…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…”
Crabtree, G. W., & Gogos, J. A. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00028 · Cited by 106
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 110
“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).”
BackgroundMethodInfluentialOxytocin 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
“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).”
BackgroundDeregulated mTOR-mediated translation in intellectual disability
Troca-Marín, J. A., Alves-Sampaio, A., & Montesinos, M. L. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.01.005 · Cited by 109
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
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 111
“The contextual fear conditioning experiment was based on the protocol used by Paradee et al. (1999).”
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
“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.”
Pop, A. S., Gomez‐Mancilla, B., Neri, G., Willemsen, R., & Gasparini, F. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3330-3 · Cited by 101
“…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).”
BackgroundResultAutism 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 103
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 95
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
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 104
“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,…”
BackgroundComplications 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
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
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 91
“…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).”
BackgroundMetabotropic Glutamate Receptors as Therapeutic Targets for Schizophrenia
Vinson, P., & Conn, P. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.005 · Cited by 95
“…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).”
BackgroundMoon, 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 91
“…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).”
BackgroundMethodResultInfluentialUnderstanding fragile X syndrome: insights from animal models
Bakker, C. E., & Oostra, B. A. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072845 · Cited by 90
“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).”
BackgroundMethodInfluentialSantos, A. R., Kanellopoulos, A. K., & Bagni, C. (2014) · Learning & Memory · doi:10.1101/lm.035956.114 · Cited by 91
“…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.”
BackgroundMethodResultInfluentialEagleson, 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 85
“…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).”
BackgroundFarzin, F., Rivera, S. M., & Hessl, D. R. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-009-0744-1 · Cited by 83
“…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).”
Qin, M., Xia, Z., Huang, T., & Smith, C. B. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.047 · Cited by 87
“…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).”
BackgroundInfluentialHippocampal 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 87
“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).”
BackgroundMethodInfluentialLoss 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
“…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).”
ResultNaturalness and Animal Welfare
Yeates, J. W. (2018) · Animals · doi:10.3390/ani8040053 · Cited by 80
Metadata
- 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.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 94
- Issue
- 1
- Pages
- 185-192
- ISSN
- 0306-4522 (ISSN-L)
- 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
- 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
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