Correction of Fragile X Syndrome in Mice

Dölen, Gül; Osterweil, Emily; Rao, B.S. Shankaranarayana; Smith, Gordon B.; Auerbach, Benjamin D.; Chattarji, Sumantra; Bear, Mark F.

doi:10.1016/j.neuron.2007.12.001

Cited by 979Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchAutism Spectrum Disorder Research

Correction of Fragile X Syndrome in Mice

Open access

Dölen, Gül, Osterweil, Emily, Rao, B.S. Shankaranarayana, Smith, Gordon B., Auerbach, Benjamin D., Chattarji, Sumantra, Bear, Mark F.·2007·Neuron

DOI 10.1016/j.neuron.2007.12.001PMC PMC2199268

Open this paper in CoChat — free account Open PDF

Abstract

Fragile X syndrome (FXS) is the most common form of heritable mental retardation and the leading identified cause of autism. FXS is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. According to one proposal, many psychiatric and neurological symptoms of FXS result from unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea we generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.neuron.2007.12.001

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

A 50% reduction in mGluR5 expression decreased excess translation and improved behavior in the fragile X mouse model.
“A 50% reduction in mGluR5 expression decreased excess translation and improved behavior in the fragile X mouse model 42 .”
From Progress toward treatments for synaptic defects in autism (2013) · cites this paper as [42]
A similar suppressor effect has been demonstrated by the decrease of abnormal behavior of the Fmr1 mutant mice carrying a heterozygous mutation of the metabotropic glutamate receptor mGluR5.
“A similar suppressor effect has been demonstrated by the decrease of abnormal behavior of the Fmr1 mutant mice carrying a heterozygous mutation of the metabotropic glutamate receptor mGluR5 [84].”
From Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders (2012) · cites this paper as [84]
These findings are the basis of human clinical trials testing mGluR5 antagonists for Fragile X syndrome.
“These findings are the basis of human clinical trials that aim to test the efficacy of mGluR5 antagonists for the treating Fragile X syndrome23,56–58.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [58]
Fmr1 mutant mice have a significant delay in the stabilization of dendritic spines and in the maturation of thalamocortical and corticocortical synapses, defects associated with a temporal shift in the critical period for sensory-induced plasticity across different cortical areas.
“Fmr1 mutant mice have a significant delay in the stabilization of dendritic spines and in the maturation of thalamocortical and corticocortical synapses 94-98 , defects associated with a temporal shift in the critical period for sensory-induced plasticity across different cortical areas 94,97,99-101 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [99]
Preclinical studies have primarily focused on mGluR5 signaling as potential targets for treatment in adult mice.
“Preclinical studies have primarily focused on mGluR5 signaling as potential targets for treatment in adult mice 99,110-113 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [99]

Reducing mGluR5 activity genetically corrects multiple phenotypes in Fmr1-knockout mice and dfmr1 mutant flies.
“Genetic reduction of mGluR5 activity achieves correction of multiple phenotypes in Fmr1-KO mice and dfmr1−/− flies26.”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [26]
Core FXS mouse deficits, including protein synthesis, dendritic spine density and morphology, long-term depression, and audiogenic seizures, are consistently rescued by more than ten genetic approaches and multiple drug classes.
“One striking conclusion of the broad array of preclinical studies is that these core deficits can be consistently rescued by more than ten genetic approaches and multiple classes of pharmacological compounds including mGluR antagonists (MPEP, fenobam, mavoglurant and CTEP), GABA agonists, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mechanistic target of rapamycin (mTOR) inhib”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [26]
In the fragile X mouse model, reducing mGluR5 expression rescued a range of phenotypes relevant to the human disorder.
“This study demonstrates in the fragile X mouse model the rescue of a range of phenotypes relevant to the human disorder by reducing mGluR5 expression.”
From Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome (2018) · cites this paper as [26]
Crossing Grm5 heterozygous mice with Fmr1 knockout mice, producing a 50% reduction in mGluR5 protein, corrected typical fragile X syndrome phenotypic features including spine dysmorphogenesis and audiogenic seizures, and restored mGluR-long-term depression.
“The resulting 50% reduction in mGluR5 protein levels in the offspring led to the correction of typical FXS phenotypic features, including spine dysmorphogenesis and audiogenic seizures, and restored mGluR-LTD (90).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [90]
Elevated mGluR5-mediated signaling and protein synthesis in fragile X knockout mice provided the rationale for testing mGluR5 antagonists in fragile X clinical trials.
“Discovery of elevated metabotropic glutamate receptor subtype 5 (mGluR5)–mediated signaling and protein synthesis in fragile X knockout mice (53–56) provided the rationale for testing mGluR5 antagonists in ongoing fragile X clinical trials.”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [54]
Several forms of NMDA-receptor-dependent plasticity are impaired by loss of FMRP, including LTP in cortex and amygdala, increased threshold for spike-timing dependent plasticity, and altered ocular dominance plasticity.
“Moreover, several forms of NMDA-receptor-dependent plasticity are impaired by loss of FMRP. LTP is abolished in cortex and amygdala (but not hippocampus), the threshold for spike-timing dependent plasticity is increased, and ocular dominance plasticity is altered (Desai et al., 2006; Dolen et al., 2007; Li et al., 2002; Meredith et al., 2007; Zhao et al., 2005).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Dolen et al., 2007

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Learning induces long-term potentiation in the hippocampus
Whitlock, J. R., Heynen, A. J., Shuler, M. G., & Bear, M. F. (2006) · Science · doi:10.1126/science.1128134 · Cited by 1,913 · see citing works
Self-citation
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
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
Self-citation
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · 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
Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression.
Huber, K., Kayser, M., & Bear, M. (2000) · Science · doi:10.1126/science.288.5469.1254 · Cited by 1,015 · see citing works
Self-citation
Mice Lacking Metabotropic Glutamate Receptor 5 Show Impaired Learning and Reduced CA1 Long-Term Potentiation (LTP) But Normal CA3 LTP
Lu, Y.-M., Jia, Z., Janus, C., Henderson, J. T., Gerlai, R., Wojtowicz, J. M., & Roder, J. C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05196.1997 · Cited by 634 · see citing works
Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium.
(1994) · PubMed · Cited by 565 · see citing works
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521 · see citing works
Pharmacological Rescue of Synaptic Plasticity, Courtship Behavior, and Mushroom Body Defects in a Drosophila Model of Fragile X Syndrome
McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D. A., Braunstein, E. M., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.038 · Cited by 473 · see citing works
Dynamic Translational and Proteasomal Regulation of Fragile X Mental Retardation Protein Controls mGluR-Dependent Long-Term Depression
Hou, L., Antion, M. D., Hu, D., Spencer, C. M., Paylor, R., & Klann, E. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.005 · Cited by 469 · 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
How Monocular Deprivation Shifts Ocular Dominance in Visual Cortex of Young Mice
Frenkel, M. Y., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.12.003 · Cited by 412 · see citing works
Self-citation
Chemical Induction of mGluR5- and Protein Synthesis–Dependent Long-Term Depression in Hippocampal Area CA1
Huber, K. M., Roder, J., & Bear, M. F. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.1.321 · Cited by 390 · see citing works
Self-citation
(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
Altered Cortical Synaptic Morphology and Impaired Memory Consolidation in Forebrain- Specific Dominant-Negative PAK Transgenic Mice
Hayashi, M. L., Choi, S.-Y., Rao, B. S. S., Jung, H.-Y., Lee, H.-K., Zhang, D., Chattarji, S., Kirkwood, A., & Tonegawa, S. (2004) · Neuron · doi:10.1016/j.neuron.2004.05.003 · Cited by 280 · see citing works
Self-citation
Postadolescent Changes in Regional Cerebral Protein Synthesis: AnIn VivoStudy in theFmr1Null Mouse
Qin, M., Kang, J., Burlin, T. V., Jiang, C., & Smith, C. B. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0093-05.2005 · Cited by 263 · see citing works
Metabotropic glutamate receptors trigger postsynaptic protein synthesis.
Weiler, I., & Greenough, W. (1993) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.90.15.7168 · Cited by 260 · see citing works
Metabotropic Glutamate Receptors Trigger Homosynaptic Protein Synthesis to Prolong Long-Term Potentiation
Raymond, C. R., Thompson, V. L., Tate, W., & Abraham, W. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-03-00969.2000 · Cited by 246 · see citing works
Selective Abolition of the NMDA Component of Long-Term Potentiation in Mice Lacking mGluR5Preprint
Jia, Z., Lu, Y., Henderson, J., Taverna, F. A., Romano, C., Abramow-Newerly, W., Wojtowicz, J. M., & Roder, J. (1998) · Learning & Memory · doi:10.1101/lm.5.4.331 · Cited by 233 · see citing works
Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons
Vanderklish, P. W., & Edelman, G. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032681099 · Cited by 194 · see citing works
Prolonged Epileptiform Discharges Induced by Altered Group I Metabotropic Glutamate Receptor-Mediated Synaptic Responses in Hippocampal Slices of a Fragile X Mouse Model
Chuang, S.-C., Zhao, W., Bauchwitz, R., Yan, Q., Bianchi, R., & Wong, R. K. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1777-05.2005 · Cited by 190 · see citing works
FMR1 Knockout mice: A model to study fragile X mental retardation
Oostra, B. A., Bakker, C. E., & Reyniers, E. (1994) · The American Journal of Human Genetics · Cited by 181 · see citing works
Local Protein Synthesis and Spine Morphogenesis: Fragile X Syndrome and Beyond
Grossman, A. W., Aldridge, G. M., Weiler, I. J., & Greenough, W. T. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1790-06.2006 · Cited by 178 · see citing works
Fmr1 KO Mice as a Possible Model of Autistic Features
Bernardet, M., & Crusio, W. E. (2006) · The Scientific World JOURNAL · doi:10.1100/tsw.2006.220 · Cited by 170 · see citing works
Metabotropic Glutamate Receptor Subtype 5 Antagonists MPEP and MTEP
Lea, P. M., & Faden, A. I. (2006) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2006.00149.x · Cited by 168 · see citing works
A Biochemical Correlate of the Critical Period for Synaptic Modification in the Visual Cortex
Dudek, S. M., & Bear, M. F. (1989) · Science · doi:10.1126/science.2573152 · Cited by 160 · see citing works
Self-citation
Anisomycin infused into the hippocampus fails to block “reconsolidation” but impairs extinction: The role of re-exposure durationPreprint
Power, A. E., Berlau, D. J., McGaugh, J. L., & Steward, O. (2006) · Learning & Memory · doi:10.1101/lm.91206 · Cited by 159 · see citing works
Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome
Tucker, B., Richards, R. I., & Lardelli, M. T. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl422 · Cited by 133 · see citing works
Requirement of Protein Synthesis for Group I mGluR-Mediated Induction of Epileptiform Discharges
Merlin, L. R., Bergold, P. J., & Wong, R. K. S. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.80.2.989 · Cited by 99 · see citing works
Fragile X: translation in action
Bear, M. F., Dölen, G., Osterweil, E., & Nagarajan, N. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301610 · Cited by 94 · see citing works
Self-citation
Rapid Ocular Dominance Plasticity Requires Cortical but Not Geniculate Protein Synthesis
Taha, S. A., & Stryker, M. P. (2002) · Neuron · doi:10.1016/s0896-6273(02)00673-6 · Cited by 91 · see citing works
The Group I Metabotropic Glutamate Receptor Agonist (S)-3,5-Dihydroxyphenylglycine Induces a Novel Form of Depotentiation in the CA1 Region of the Hippocampus
Zho, W.-M., You, J.-L., Huang, C., & Hsu, K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08838.2002 · Cited by 81 · see citing works
Expression of metabotropic glutamate receptors in the rat and human testis
Storto, M., Sallese, M., Salvatore, L., Poulet, R., Condorelli, D. F., Dell’Albani, P., Marcello, M. F., Romeo, R., Piomboni, P., Barone, N., et al. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1700071 · Cited by 81 · see citing works
Induction of Long-Term Depression in Cerebellar Purkinje Cells Requires a Rapidly Turned Over Protein
Karachot, L., Shirai, Y., Vigot, R., Yamamori, T., & Ito, M. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.1.280 · Cited by 74 · see citing works
Evidence that the metabotropic glutamate receptor 5 antagonist MPEP may act as an inhibitor of the norepinephrine transporter in vitro and in vivo
Heidbreder, C. A., Bianchi, M., Lacroix, L. P., Faedo, S., Perdonà, E., Remelli, R., Cavanni, P., & Crespi, F. (2003) · Synapse · doi:10.1002/syn.10261 · Cited by 74 · see citing works
Growth in stature in fragile X families: A mixed longitudinal study
Loesch, D. Z., Huggins, R., & Hoang, N. H. (1995) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320580311 · Cited by 52 · see citing works
Audiogenic seizures: Increased benzodiazepin receptor binding in a susceptible strain of mice
Robertson, H. A. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90149-1 · Cited by 38 · see citing works
The Phylogenetic Relationship of the Glutamate and Pheromone G‐Protein‐Coupled Receptors in Different Vertebrate Species
Bjarnadóttir, T. K., Schiöth, H. B., & Fredriksson, R. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1327.031 · Cited by 8 · see citing works

Flagged first, then by citations

Sorted by citations

Advances in autism genetics: on the threshold of a new neurobiology
Abrahams, B. S., & Geschwind, D. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2346 · Cited by 1,866 · see citing works
Dendritic spine pathology in neuropsychiatric disorders
Penzes, P., Cahill, M. E., Jones, K. A., VanLeeuwen, J.-E., & Woolfrey, K. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2741 · Cited by 1,523 · see citing works
De Novo Gene Disruptions in Children on the Autistic Spectrum
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.-H., Narzisi, G., Leotta, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.009 · Cited by 1,446 · see citing works
Behavioural phenotyping assays for mouse models of autism
Silverman, J. L., Yang, M., Lord, C., & Crawley, J. N. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2851 · Cited by 1,462 · see citing works
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.034 · Cited by 1,149 · see citing works
Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits
Peñagarikano, O., Abrahams, B. S., Herman, E. I., Winden, K. D., Gdalyahu, A., Dong, H., Sonnenblick, L. I., Gruver, R., Almajano, J., Bragin, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.040 · Cited by 1,075 · see citing works
Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051 · see citing works
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Long-term depression in the CNS
Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2867 · Cited by 926 · see citing works
Fragile X syndrome
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797 · see citing works
Self-citation
Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C.-F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A., & Sheng, M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.005 · Cited by 735 · see citing works
Activity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666 · see citing works
The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc
Greer, P. L., Hanayama, R., Bloodgood, B. L., Mardinly, A. R., Lipton, D. M., Flavell, S. W., Kim, T.-K., Griffith, E. C., Waldon, Z., Maehr, R., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.026 · Cited by 30 · see citing works
A synaptic trek to autism
Bourgeron, T. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.003 · Cited by 637 · see citing works
Common circuit defect of excitatory-inhibitory balance in mouse models of autism
Gogolla, N., LeBlanc, J. J., Quast, K. B., Südhof, T. C., Fagiolini, M., & Hensch, T. K. (2009) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9023-x · Cited by 610 · see citing works
The Fragile X Syndrome Protein Represses Activity-Dependent Translation through CYFIP1, a New 4E-BP
Napoli, I., Mercaldo, V., Boyl, P. P., Eleuteri, B., Zalfa, F., De Rubeis, S., Di Marino, D., Mohr, E., Massimi, M., Falconi, M., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.031 · Cited by 609 · see citing works
Group 1 mGluR-Dependent Synaptic Long-Term Depression: Mechanisms and Implications for Circuitry and Disease
Lüscher, C., & Huber, K. M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.016 · Cited by 627 · see citing works
The Autistic Neuron: Troubled Translation?
Kelleher, R. J., & Bear, M. F. (2008) · Cell · doi:10.1016/j.cell.2008.10.017 · Cited by 598 · see citing works
Self-citation
Epigenetic Modification of the FMR1 Gene in Fragile X Syndrome Is Associated with Differential Response to the mGluR5 Antagonist AFQ056
Jacquemont, S., Curie, A., des Portes, V., Torrioli, M. G., Berry-Kravis, E., Hagerman, R. J., Ramos, F. J., Cornish, K., He, Y., Paulding, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001708 · Cited by 609 · see citing works
Mutations causing syndromic autism define an axis of synaptic pathophysiology
Auerbach, B. D., Osterweil, E. K., & Bear, M. F. (2011) · Nature · doi:10.1038/nature10658 · Cited by 592 · see citing works
Self-citation
Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders
Lee, E., Lee, J., & Kim, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.011 · Cited by 468 · see citing works
Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex
Sipe, G. O., Lowery, Tremblay, M.-È., Kelly, E. A., Lamantia, C. E., & Majewska, A. K. (2016) · Nature Communications · doi:10.1038/ncomms10905 · Cited by 512 · see citing works
Advances in Autism
Geschwind, D. H. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.053107.121225 · Cited by 512 · see citing works
Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice
Michalon, A., Sidorov, M., Ballard, T. M., Ozmen, L., Spooren, W., Wettstein, J. G., Jaeschke, G., Bear, M. F., & Lindemann, L. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.009 · Cited by 489 · see citing works
Self-citation
Early Brain Overgrowth in Autism Associated With an Increase in Cortical Surface Area Before Age 2 Years
Hazlett, H. C., Poe, M. D., Gerig, G., Styner, M., Chappell, C., Smith, R. G., Vachet, C., & Piven, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.39 · Cited by 481 · see citing works
The translation of translational control by FMRP: therapeutic targets for FXS
Darnell, J. C., & Klann, E. (2013) · Nature Neuroscience · doi:10.1038/nn.3379 · Cited by 491 · see citing works
Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders
Leblond, C. S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., Konyukh, M., Chaste, P., Ey, E., Rastam, M., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002521 · Cited by 429 · see citing works
Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models
Antoine, M. W., Langberg, T., Schnepel, P., & Feldman, D. E. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.026 · Cited by 413 · see citing works
Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP
Silverman, J. L., Tolu, S. S., Barkan, C. L., & Crawley, J. N. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.201 · Cited by 438 · see citing works
A pilot open label, single dose trial of fenobam in adults with fragile X syndrome
Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., Hutchison, J., Snape, M., Tranfaglia, M., Nguyen, D. V., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.063701 · Cited by 411 · see citing works
Failure of neuronal homeostasis results in common neuropsychiatric phenotypes
Ramocki, M. B., & Zoghbi, H. Y. (2008) · Nature · doi:10.1038/nature07457 · Cited by 399 · see citing works
Therapeutic potential of mood stabilizers lithium and valproic acid:Beyond bipolar disorder
Chiu, C.-T., Wang, Z., Hunsberger, J. G., & Chuang, D.-M. (2013) · Pharmacological Reviews · doi:10.1124/pr.111.005512 · Cited by 404 · see citing works
Developmental timing and critical windows for the treatment of psychiatric disorders
Marín, O. (2016) · Nature Medicine · doi:10.1038/nm.4225 · Cited by 374 · see citing works
The BCM theory of synapse modification at 30: interaction of theory with experiment
Cooper, L. N., & Bear, M. F. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3353 · Cited by 395 · see citing works
Self-citation
Hypersensitivity to mGluR5 and ERK1/2 Leads to Excessive Protein Synthesis in the Hippocampus of a Mouse Model of Fragile X Syndrome
Osterweil, E. K., Krueger, D. D., Reinhold, K., & Bear, M. F. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3888-10.2010 · Cited by 384 · see citing works
Self-citation
The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)
Bhakar, A. L., Dölen, G., & Bear, M. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153138 · Cited by 370 · see citing works
Self-citation
Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
Berry-Kravis, E. M., Lindemann, L., Jønch, A. E., Apostol, G., Bear, M. F., Carpenter, R. L., Crawley, J. N., Curie, A., Des Portes, V., Hossain, F., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.221 · Cited by 336 · see citing works
Self-citation
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Bagni, C., Tassone, F., Neri, G., & Hagerman, R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63141 · Cited by 321 · see citing works
Delayed Stabilization of Dendritic Spines in Fragile X Mice
Cruz-Martin, A., Crespo, M., & Portera-Cailliau, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0577-10.2010 · Cited by 321 · see citing works
Genetic Removal of p70 S6 Kinase 1 Corrects Molecular, Synaptic, and Behavioral Phenotypes in Fragile X Syndrome Mice
Bhattacharya, A., Kaphzan, H., Alvarez-Dieppa, A. C., Murphy, J. P., Pierre, P., & Klann, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.022 · Cited by 316 · see citing works
Autism: A “Critical Period” Disorder?
LeBlanc, J. J., & Fagiolini, M. (2011) · Neural Plasticity · doi:10.1155/2011/921680 · Cited by 301 · see citing works
Striatal Circuits as a Common Node for Autism Pathophysiology
Fuccillo, M. V. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00027 · Cited by 269 · see citing works
Dysregulation and restoration of translational homeostasis in fragile X syndrome
Richter, J. D., Bassell, G. J., & Klann, E. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4001 · Cited by 275 · see citing works
Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice
Harlow, E. G., Till, S. M., Russell, T. A., Wijetunge, L. S., Kind, P., & Contractor, A. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.024 · Cited by 252 · see citing works
The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology
Chen, J. A., Peñagarikano, O., Belgard, T. G., Swarup, V., & Geschwind, D. H. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040405 · Cited by 254 · see citing works
Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders
Sebat, J., Levy, D. L., & McCarthy, S. E. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.10.004 · Cited by 260 · see citing works
Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486
Dolan, B. M., Duron, S. G., Campbell, D. A., Vollrath, B., Rao, B. S. S., Ko, H.-Y., Lin, G. G., Govindarajan, A., Choi, S.-Y., & Tonegawa, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219383110 · Cited by 260 · see citing works
Self-citation
Toward Fulfilling the Promise of Molecular Medicine in Fragile X Syndrome
Krueger, D. D., & Bear, M. F. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-061109-134644 · Cited by 259 · see citing works
Self-citation
Fragile X and autism: intertwined at the molecular level leading to targeted treatments
Hagerman, R., Hoem, G., & Hagerman, P. (2010) · Molecular Autism · doi:10.1186/2040-2392-1-12 · Cited by 247 · see citing works
Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism
Silverman, J. L., Smith, D. G., Rizzo, S. J. S., Karras, M. N., Turner, S. M., Tolu, S. S., Bryce, D. K., Smith, D. L., Fonseca, K., Ring, R. H., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003501 · Cited by 251 · see citing works
Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome
Ronesi, J. A., Collins, K. A., Hays, S. A., Tsai, N.-P., Guo, W., Birnbaum, S. G., Hu, J.-H., Worley, P. F., Gibson, J. R., & Huber, K. M. (2012) · Nature Neuroscience · doi:10.1038/nn.3033 · Cited by 251 · see citing works
Reversal of Disease-Related Pathologies in the Fragile X Mouse Model by Selective Activation of GABA B Receptors with Arbaclofen
Henderson, C., Wijetunge, L., Kinoshita, M. N., Shumway, M., Hammond, R. S., Postma, F. R., Brynczka, C., Rush, R., Thomas, A., Paylor, R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004218 · Cited by 249 · see citing works
Self-citation
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
Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome
Gross, C., Nakamoto, M., Yao, X., Chan, C.-B., Yim, S. Y., Ye, K., Warren, S. T., & Bassell, G. J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0402-10.2010 · Cited by 241 · 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
Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms
Gladding, C. M., Fitzjohn, S. M., & Molnár, E. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001735 · Cited by 233 · see citing works
Progress toward treatments for synaptic defects in autism
Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218 · see citing works
Rethinking Mental Illness
Insel, T. R. (2010) · JAMA · doi:10.1001/jama.2010.555 · Cited by 224 · see citing works
Reversing Neurodevelopmental Disorders in Adults
Ehninger, D., Li, W., Fox, K., Stryker, M. P., & Silva, A. J. (2008) · Neuron · doi:10.1016/j.neuron.2008.12.007 · Cited by 196 · 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
Genetics of intellectual disability
Ropers, H. H. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.07.008 · Cited by 199 · see citing works
Fragile X: Leading the Way for Targeted Treatments in Autism
Wang, L. W., Berry-Kravis, E., & Hagerman, R. J. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.005 · Cited by 176 · see citing works
Reversion of FMR1 methylation and silencing by editing the triplet repeats in Fragile X iPSC-derived neurons
Park, C.-Y., Halevy, T., Lee, D. R., Sung, J. J., Lee, J. S., Yanuka, O., Benvenisty, N., & Kim, D.-W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.084 · Cited by 178 · see citing works
No Change in the Age of Diagnosis for Fragile X Syndrome: Findings From a National Parent Survey
Bailey, D. B., Raspa, M., Bishop, E., & Holiday, D. (2009) · Pediatrics · doi:10.1542/peds.2008-2992 · Cited by 175 · see citing works
Fragile X syndrome: a review of clinical and molecular diagnoses
Ciaccio, C., Fontana, L., Milani, D., Tabano, S., Miozzo, M., & Esposito, S. (2017) · Italian Journal of Pediatrics · doi:10.1186/s13052-017-0355-y · Cited by 160 · see citing works
The genetics of child psychiatric disorders: focus on autism and Tourette syndrome
State, M. W. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.004 · Cited by 162 · see citing works
Fragile X mental retardation protein regulates protein expression and mRNA translation of the potassium channel Kv4.2
Gross, C., Yao, X., Pong, D. L., Jeromin, A., & Bassell, G. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6661-10.2011 · Cited by 161 · see citing works
Convulsing toward the pathophysiology of autism
Tuchman, R., Moshé, S. L., & Rapin, I. (2009) · Brain and Development · doi:10.1016/j.braindev.2008.09.009 · Cited by 142 · 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
A mouse model of the human Fragile X syndrome I304N mutation
Zang, J. B., Nosyreva, E. D., Spencer, C. M., Volk, L. J., Musunuru, K., Zhong, R., Stone, E. F., Yuva-Paylor, L. A., Huber, K. M., Paylor, R., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000758 · Cited by 138 · see citing works
Metabotropic Glutamate Receptor 5 Upregulation in Children with Autism is Associated with Underexpression of Both Fragile X Mental Retardation Protein and GABAA Receptor Beta 3 in Adults with Autism
Fatemi, S. H., Folsom, T. D., Kneeland, R. E., & Liesch, S. B. (2011) · The Anatomical Record · doi:10.1002/ar.21299 · Cited by 137 · see citing works
Increased GABAB Receptor-Mediated Signaling Reduces the Susceptibility of Fragile X Knockout Mice to Audiogenic Seizures
Pacey, L. K. K., Heximer, S. P., & Hampson, D. R. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056127 · Cited by 133 · see citing works
Effect of the mGluR5-NAM Basimglurant on Behavior in Adolescents and Adults with Fragile X Syndrome in a Randomized, Double-Blind, Placebo-Controlled Trial: FragXis Phase 2 Results
FragXis Study Group, Youssef, E. A., Berry-Kravis, E., Czech, C., Hagerman, R. J., Hessl, D., Wong, C. Y., Rabbia, M., Deptula, D., John, A., et al. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.177 · Cited by 133 · see citing works
α-Tocopherol Protects Against Oxidative Stress in the Fragile X Knockout Mouse: an Experimental Therapeutic Approach for the Fmr1 Deficiency
de Diego-Otero, Y., Romero-Zerbo, Y., Bekay, R. E., Decara, J., Sanchez, L., Fonseca, F. R.-D., & Arco-Herrera, I. D. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.152 · Cited by 133 · see citing works
The NIH Toolbox Cognitive Battery for intellectual disabilities: Three preliminary studies and future directions
Hessl, D., Sansone, S. M., Berry-Kravis, E., Riley, K., Widaman, K. F., Abbeduto, L., Schneider, A., Coleman, J., Oaklander, D., Rhodes, K. C., et al. (2016) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9167-4 · Cited by 126 · see citing works
Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders
Santini, E., & Klann, E. (2014) · Science Signaling · doi:10.1126/scisignal.2005832 · Cited by 118 · see citing works
Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments
Veenstra-VanderWeele, J., & Blakely, R. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.185 · 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
Drug targets for cognitive enhancement in neuropsychiatric disorders.
Wallace, T. L., Ballard, T. M., Pouzet, B., Riedel, W. J., & Wettstein, J. G. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.03.022 · Cited by 127 · see citing works
Neuronal connectivity as a convergent target of gene × environment interactions that confer risk for Autism Spectrum Disorders
Stamou, M., Streifel, K. M., Goines, P. E., & Lein, P. J. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.12.001 · Cited by 128 · see citing works
Glutamate mediated signaling in the pathophysiology of autism spectrum disorders
Choudhury, P. R., Lahiri, S., & Rajamma, U. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.06.023 · Cited by 121 · see citing works
Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome
Gross, C., Chang, C.-W., Kelly, S. M., Bhattacharya, A., McBride, S. M. J., Danielson, S. W., Jiang, M. Q., Chan, C. B., Ye, K., Gibson, J. R., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.060 · Cited by 117 · see citing works
From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis
Ehninger, D., De Vries, P. J., & Silva, A. J. (2009) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2009.01208.x · Cited by 120 · see citing works
Synapse dysfunction in autism: a molecular medicine approach to drug discovery in neurodevelopmental disorders
Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.09.004 · Cited by 119 · see citing works
High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism
Kelleher III, R. J., Geigenmüller, U., Hovhannisyan, H., Trautman, E., Pinard, R., Rathmell, B., Carpenter, R., & Margulies, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035003 · Cited by 116 · see citing works
Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion
Tian, D., Stoppel, L. J., Heynen, A. J., Lindemann, L., Jaeschke, G., Mills, A. A., & Bear, M. F. (2015) · Nature Neuroscience · doi:10.1038/nn.3911 · Cited by 109 · see citing works
Self-citation
Brain Volume Findings in 6-Month-Old Infants at High Familial Risk for Autism
Hazlett, H. C., Gu, H., McKinstry, R. C., Shaw, D. W. W., Botteron, K. N., Dager, S. R., Styner, M., Vachet, C., Gerig, G., Paterson, S. J., et al. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11091425 · Cited by 108 · see citing works
Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00781.x · Cited by 108 · see citing works
Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice
Westmark, C. J., Westmark, P. R., O'Riordan, K. J., Ray, B. C., Hervey, C. M., Salamat, M. S., Abozeid, S. H., Stein, K. M., Stodola, L. A., Tranfaglia, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026549 · Cited by 110 · see citing works
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
Self-citation
Drug discovery for autism spectrum disorder: challenges and opportunities
Ghosh, A., Michalon, A., Lindemann, L., Fontoura, P., & Santarelli, L. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4102 · Cited by 108 · see citing works
Social peers rescue autism‐relevant sociability deficits in adolescent mice
Yang, M., Perry, K., Weber, M. D., Katz, A. M., & Crawley, J. N. (2011) · Autism Research · doi:10.1002/aur.163 · Cited by 106 · 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
Selective deletion of astroglial FMRP dysregulates glutamate transporter GLT1 and contributes to fragile X syndrome phenotypes in vivo.
Higashimori, H., Schin, C. S., Chiang, M. S. R., Morel, L., Shoneye, T. A., Nelson, D. L., & Yang, Y. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1069-16.2016 · Cited by 105 · see citing works
Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice.
Dansie, L. E., Phommahaxay, K., Okusanya, A. G., Uwadia, J., Huang, M., Rotschafer, S. E., Razak, K. A., Ethell, D. W., & Ethell, I. M. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.058 · Cited by 95 · see citing works
Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice
Gantois, I., Pop, A. S., de Esch, C. E. F., Buijsen, R. A. M., Pooters, T., Gomez-Mancilla, B., Gasparini, F., Oostra, B. A., D’Hooge, R., & Willemsen, R. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.10.059 · Cited by 100 · see citing works
R-Baclofen reverses cognitive deficits and improves social interactions in two lines of 16p11.2 deletion mice
Stoppel, L. J., Kazdoba, T. M., Schaffler, M. D., Preza, A. R., Heynen, A., Crawley, J. N., & Bear, M. F. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.236 · Cited by 92 · see citing works
Self-citation
Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model
Monyak, R. E., Emerson, D., Schoenfeld, B. P., Zheng, X., Chambers, D. B., Rosenfelt, C., Langer, S., Hinchey, P., Choi, C. H., McDonald, T. V., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.51 · Cited by 100 · see citing works
Cellular and synaptic network defects in autism
Peça, J., & Feng, G. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.02.015 · Cited by 96 · see citing works

Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers
Kenneson, A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.14.1449 · Cited by 456 · see citing works
The role of fragile X mental retardation protein in major mental disorders
Fatemi, S. H., & Folsom, T. D. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.011 · Cited by 80 · see citing works
Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium.
(1994) · PubMed · Cited by 565 · see citing works
Serotonin dysregulation in Fragile X Syndrome: implications for treatment
Hanson, A. C., & Hagerman, R. J. (2014) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2014.01027 · Cited by 40 · see citing works
Newborn, Carrier, and Early Childhood Screening Recommendations for Fragile X
Abrams, L. J., Cronister, A., Brown, W. T., Tassone, F., Sherman, S. L., Finucane, B. M., McConkie‐Rosell, A., Hagerman, R. J., Kaufmann, W. E., Picker, J. D., et al. (2012) · PEDIATRICS · doi:10.1542/peds.2012-0693 · Cited by 41 · see citing works

Authors: Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F.
Affiliations: Howard Hughes Medical Institute (US)
National Institute of Mental Health and Neurosciences (IN)
Tata Institute of Fundamental Research (IN)
Corresponding author: Bear, Mark F.
ORCID: Dölen, Gül
Osterweil, Emily
Rao, B.S. Shankaranarayana
Auerbach, Benjamin D.
Chattarji, Sumantra
Bear, Mark F.
Venue: Neuron
Publisher: Elsevier BV
Published: 2007-12
Volume: 56
Issue: 6
Pages: 955-962
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2007.12.001
PMC: PMC2199268
OpenAlex: W2084889756
Cited by: 979
References: 39
Citations by year: 2026: 19 · 2025: 26 · 2024: 19 · 2023: 26 · 2022: 30 · 2021: 42 · 2020: 44 · 2019: 41 · 2018: 35 · 2017: 57 · 2016: 62 · 2015: 73 · 2014: 65 · 2013: 81 · 2012: 87
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2055 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders: Simons Foundation
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institute of Mental Health
FRAXA Research Foundation
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 › Autism Spectrum Disorder Research
Keywords: fragile X syndrome, FMRP, FMR1 gene silencing, mGluR5, metabotropic glutamate receptors, autism spectrum disorder, intellectual disability, pathogenesis, therapeutic target
MeSH terms: Acoustic Stimulation, Animals, Behavior, Animal, Disease Models, Animal, Fragile X Syndrome, Gene Expression Regulation, Heterozygote, Functional Laterality, Learning, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Phenotype, Seizures, Visual Cortex, Multivariate Analysis, Receptors, Metabotropic Glutamate, Mice, Knockout, Mice, Fragile X Messenger Ribonucleoprotein 1, Receptor, Metabotropic Glutamate 5

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

Correction of Fragile X Syndrome in Mice

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks