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Correction of Fragile X Syndrome in Mice
Open accessAbstract
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.
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In the citing paper
“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
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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 citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
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Citations
Cites
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
Self-citationThe 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
Self-citationAltered 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
Self-citationBrown, 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
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,108
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
Self-citationLu, 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
(1994) · PubMed · Cited by 565
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
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 484
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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
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
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
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
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
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
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
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
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
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
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797
Self-citationRegulation 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
Activity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666
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
Bourgeron, T. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.003 · Cited by 637
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
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
Lüscher, C., & Huber, K. M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.016 · Cited by 627
The Autistic Neuron: Troubled Translation?
Kelleher, R. J., & Bear, M. F. (2008) · Cell · doi:10.1016/j.cell.2008.10.017 · Cited by 598
Self-citationJacquemont, 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
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
Self-citationExcitation/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
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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
Geschwind, D. H. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.053107.121225 · Cited by 512
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
Self-citationHazlett, 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
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
Antoine, M. W., Langberg, T., Schnepel, P., & Feldman, D. E. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.026 · Cited by 413
Silverman, J. L., Tolu, S. S., Barkan, C. L., & Crawley, J. N. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.201 · Cited by 438
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
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Ramocki, M. B., & Zoghbi, H. Y. (2008) · Nature · doi:10.1038/nature07457 · Cited by 399
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Self-citationOsterweil, 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
Self-citationThe 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
Self-citationDrug development for neurodevelopmental disorders: lessons learned from fragile X syndrome
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Self-citationFragile 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
Berry-Kravis, E. M., Hessl, D., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D. V., Gonzalez-Heydrich, J., Wang, P. P., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004214 · Cited by 328
Self-citationDelayed 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
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
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LeBlanc, J. J., & Fagiolini, M. (2011) · Neural Plasticity · doi:10.1155/2011/921680 · Cited by 301
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
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
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
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
Sebat, J., Levy, D. L., & McCarthy, S. E. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.10.004 · Cited by 260
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
Self-citationToward 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
Self-citationSilverman, 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
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
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
Self-citationFragile X and autism: intertwined at the molecular level leading to targeted treatments
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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
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
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
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Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218
Insel, T. R. (2010) · JAMA · doi:10.1001/jama.2010.555 · Cited by 224
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
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Bureau, I., Shepherd, G. M. G., & Svoboda, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1076-08.2008 · Cited by 201
Genetics of intellectual disability
Ropers, H. H. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.07.008 · Cited by 199
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
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
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
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
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
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
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
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
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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
Fatemi, S. H., Folsom, T. D., Kneeland, R. E., & Liesch, S. B. (2011) · The Anatomical Record · doi:10.1002/ar.21299 · Cited by 137
Pacey, L. K. K., Heximer, S. P., & Hampson, D. R. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.056127 · Cited by 133
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
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
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
“Recent advances in understanding the molecular mechanisms underlying NDD through animal models [2–5] have led to targeted controlled trials with pharmacological agents designed to normalize molecular abnormalities, synaptic function, cognition, and behavior in humans with these conditions.”
BackgroundVeenstra-VanderWeele, J., & Blakely, R. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.185 · Cited by 128
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
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
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
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
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
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
Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.09.004 · Cited by 119
Santini, E., & Klann, E. (2014) · Science Signaling · doi:10.1126/scisignal.2005832 · Cited by 118
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
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
Self-citationBrain 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
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
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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
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
Self-citationDrug 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
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
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
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
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
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
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
Self-citationMonyak, 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
Metadata
- 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
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 56
- Issue
- 6
- Pages
- 955-962
- ISSN
- 0896-6273 (ISSN-L)
- 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
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