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.

doi:10.1111/j.1601-183x.2012.00781.x

Cited by 108Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchAutism Spectrum Disorder Research

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Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model

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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.xPMC PMC3922131

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Abstract

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work shows that FMRP interacts with the transcript encoding striatal‐enriched protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn and Pyk2, and subunits of N‐methyl‐d‐aspartate (NMDA) and AMPA receptors. Here, we show that basal levels of STEP are elevated and mGluR‐dependent STEP synthesis is absent in Fmr1KO mice. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1KO mice and assessed mice in a battery of behavioral tests. In addition to attenuating audiogenic seizures and seizure‐induced c‐Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1KO mice reversed characteristic social abnormalities, including approach, investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety‐related behaviors in Fmr1KO mice, such as light‐side exploration in the light/dark box. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores select social and nonsocial anxiety‐related behaviors in Fmr1KO mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS.

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STEP is upregulated in fragile X syndrome, and genetic reduction of STEP diminished seizures and restored selected social and nonsocial anxiety-related behaviors in Fmr1 knockout mice.
“Recently, the striatal enriched protein tyrosine phosphatase (STEP) has been shown to be upregulated in FXS, and genetic reduction of STEP diminished seizures and restored selected social and nonsocial anxiety-related behaviors in the Fmr1 KO mice (94).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [94]
Because STEP acts on ERK1/2, NMDA, and AMPA, which are affected in fragile X syndrome, inhibiting STEP may be considered for treating patients with fragile X syndrome.
“Because STEP acts on at least three molecules (ERK1/2, NMDA, and AMPA) affected in FXS, strategies to inhibit STEP activity may be considered for treating patients with FXS.”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [94]

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FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072
Mapping Patterns of c- fos Expression in the Central Nervous System After Seizure
Morgan, J. I., Cohén, D., Hempstead, J. L., & Curran, T. (1987) · Science · doi:10.1126/science.3037702 · Cited by 1,786
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
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 2×
“…and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society strengthening by promoting NMDAR internalization and inactivating ERK1/2, Fyn and Pyk2 (Nguyen et al. 2002; Pelkey et al. 2002; Paul et al. 2003; Snyder et al. 2005; Venkitaramani et al. 2011).”
BackgroundSelf-citation
Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines
Crawley, J. N., & Goodwin, F. K. (1980) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(80)90067-2 · Cited by 1,432
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
Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5401 · Cited by 1,046
Correction of Fragile X Syndrome in Mice
Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F. (2007) · Neuron · doi:10.1016/j.neuron.2007.12.001 · Cited by 979
Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function
Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., & Darnell, R. B. (2001) · Cell · doi:10.1016/s0092-8674(01)00566-9 · Cited by 952
Ethologically-based animal models of anxiety disorders.
Lister, R. (1990) · Pharmacology and Therapeutics · doi:10.1016/0163-7258(90)90021-s · Cited by 894
Ethopharmacological analysis of rat behavior on the elevated plus-maze
Cruz, A. P. D. M., Frei, F., & Graeff, F. G. (1994) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(94)90472-3 · Cited by 822
Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety
Rodgers, R. J., & Johnson, N. J. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00138-m · Cited by 793
Activation of in the brain
Herrera, D., & Robertson, H. A. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00021-4 · Cited by 713
Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety
Thomas, A., Burant, A., Bui, N., Graham, D., Yuva-Paylor, L. A., & Paylor, R. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1466-y · Cited by 698
The Fragile X Syndrome Protein FMRP Associates with BC1 RNA and Regulates the Translation of Specific mRNAs at Synapses
Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B., & Bagni, C. (2003) · Cell · doi:10.1016/s0092-8674(03)00079-5 · Cited by 676
The protein product of the fragile X gene, FMR1, has characteristics of an RNA-binding protein.
Siomi, H., Siomi, M. C., Nussbaum, R. L., & Dreyfuss, G. (1993) · Cell · doi:10.1016/0092-8674(93)90420-u · Cited by 641
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
Automated Three‐Chambered Social Approach Task for Mice
Yang, M., Silverman, J. L., & Crawley, J. N. (2011) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0826s56 · Cited by 598
Evidence that fragile X mental retardation protein is a negative regulator of translation
Laggerbauer, B. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.4.329 · Cited by 571
Mouse Behavioral Assays Relevant to the Symptoms of Autism*
Crawley, J. N. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00096.x · Cited by 541 · cited 1×
“We evaluated sociability using a three-chambered social choice task (Crawley 2007; Moy et al. 2009).”
Method
Imbalance of Neocortical Excitation and Inhibition and Altered UP States Reflect Network Hyperexcitability in the Mouse Model of Fragile X Syndrome
Gibson, J. R., Bartley, A. F., Hays, S. A., & Huber, K. M. (2008) · Journal of Neurophysiology · doi:10.1152/jn.90752.2008 · Cited by 529
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
Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD
Park, S., Park, J. M., Kim, S., Kim, J.-A., Shepherd, J. D., Smith-Hicks, C. L., Chowdhury, S., Kaufmann, W., Kuhl, D., Ryazanov, A. G., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.023 · Cited by 516
Evaluation of marble-burying behavior as a model of anxiety
Njung'e, K., & Handley, S. L. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90590-x · Cited by 487
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
Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model
Bilousova, T. V., Dansie, L., Ngo, M., Aye, J., Charles, J. R., Ethell, D. W., & Ethell, I. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061796 · Cited by 465
Dysregulated Metabotropic Glutamate Receptor-Dependent Translation of AMPA Receptor and Postsynaptic Density-95 mRNAs at Synapses in a Mouse Model of Fragile X Syndrome
Muddashetty, R. S., Kelić, S., Gross, C., Xu, M., & Bassell, G. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0937-07.2007 · Cited by 421
Biochemical characterization of a filtered synaptoneurosome preparation from guinea pig cerebral cortex: cyclic adenosine 3':5'-monophosphate- generating systems, receptors, and enzymes
Hollingsworth, E. B., McNeal, E., Burton, J. L., Williams, R., Daly, J. W., & Creveling, C. R. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-08-02240.1985 · Cited by 408
Autism Profiles of Males With Fragile X Syndrome
Harris, S. W., Hessl, D., Goodlin-Jones, B., Ferranti, J., Bacalman, S., Barbato, I., Tassone, F., Hagerman, P. J., Herman, K., & Hagerman, R. J. (2008) · American Journal on Mental Retardation · doi:10.1352/2008.113:427-438 · Cited by 396
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
Altered anxiety‐related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome
Spencer, C. M., Alekseyenko, O., Serysheva, E., Yuva‐Paylor, L. A., & Paylor, R. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00123.x · Cited by 349
NMDA-mediated activation of the tyrosine phosphatase STEP regulates the duration of ERK signaling
Paul, S., Nairn, A. C., Wang, P., & Lombroso, P. J. (2002) · Nature Neuroscience · doi:10.1038/nn989 · Cited by 324
Self-citation
The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development
Lu, R., Wang, H., Liang, Z., Ku, L., O'Donnell, W. T., Li, W., Warren, S. T., & Feng, Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404995101 · Cited by 322
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice
de Vrij, F. M. S., Levenga, J., van der Linde, H. C., Koekkoek, S. K., De Zeeuw, C. I., Nelson, D. L., Oostra, B. A., & Willemsen, R. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.04.002 · Cited by 313
Defective GABAergic Neurotransmission and Pharmacological Rescue of Neuronal Hyperexcitability in the Amygdala in a Mouse Model of Fragile X Syndrome
Olmos-Serrano, J. L., Paluszkiewicz, S. M., Martin, B. S., Kaufmann, W. E., Corbin, J. G., & Huntsman, M. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1714-10.2010 · Cited by 309
Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome
Restivo, L., Ferrari, F., Passino, E., Sgobio, C., Bock, J., Oostra, B. A., Bagni, C., & Ammassari-Teule, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504984102 · Cited by 299
FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein
Westmark, C. J., & Malter, J. S. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050052 · Cited by 296 · cited 4×
“…but not cytosolic, fractions and that mGluR-stimulated synthesis of STEP is absent in Fmr1KO mice, consistent with impaired mGluR-induced dendritic translation of FMRP targets (Zalfa et al. 2003; Lu et al. 2004; Hou et al. 2006; Muddashetty et al. 2007; Westmark & Malter 2007; Park et al. 2008).”
BackgroundInfluential
Social Dominance in Inbred Mouse Strains
Lindzey, G. E., Winston, H. D., & Manosevitz, M. (1961) · Nature · doi:10.1038/191474a0 · Cited by 290
Audiogenic Seizures Susceptibility in Transgenic Mice with Fragile X Syndrome
Musumeci, S. A., Bosco, P., Calabrese, G., Bakker, C., De Sarro, G. B., Elia, M., Ferri, R., & Oostra, B. A. (2000) · Epilepsia · doi:10.1111/j.1528-1157.2000.tb01499.x · Cited by 289
(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
The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95
Todd, P. K., Mack, K. J., & Malter, J. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336265100 · Cited by 280
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
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
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
Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications.
Chen, X., Mariappan, S. V. S., Catasti, P., Ratliff, R. L., Moyzis, R. K., Laayoun, A., Smith, S. S., Bradbury, E. M., & Gupta, G. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.5199 · Cited by 227
Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic‐like responses
Spencer, C. M., Alekseyenko, O. V., Hamilton, S. M., Thomas, A. M., Serysheva, E., Yuva‐Paylor, L. A., & Paylor, R. E. (2011) · Autism Research · doi:10.1002/aur.168 · Cited by 225
GSK3 Influences Social Preference and Anxiety-Related Behaviors during Social Interaction in a Mouse Model of Fragile X Syndrome and Autism
Mines, M. A., Yuskaitis, C. J., King, M. K., Beurel, E., & Jope, R. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009706 · Cited by 220
Genetic Inactivation of the NMDA Receptor NR2A Subunit has Anxiolytic- and Antidepressant-Like Effects in Mice
Boyce‐Rustay, J. M., & Holmes, A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301039 · Cited by 212
Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses
Weiler, I. J., Spangler, C. C., Klintsova, A. Y., Grossman, A. W., Kim, S. H., Bertaina-Anglade, V., Khaliq, H., de Vries, F. E., Lambers, F. A. E., Hatia, F., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407533101 · Cited by 210
Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation
Pelkey, K. A., Askalan, R., Paul, S., Kalia, L. V., Nguyen, T.-H., Pitcher, G. M., Salter, M. W., & Lombroso, P. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)00633-5 · Cited by 208
Self-citation
Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase
Boulanger, L. M., Lombroso, P., Raghunathan, A., During, M. J., Wahle, P., & Naegele, J. R. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-02-01532.1995 · Cited by 202
Self-citation
Phospho-regulation of synaptic and extrasynaptic N-methyl-d-aspartate receptors in adult hippocampal slices
Goebel-Goody, S. M., Davies, K. D., Linger, R. M. A., Freund, R. K., & Browning, M. D. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.11.006 · Cited by 194
Self-citation
Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of Fragile X syndrome
Yuskaitis, C. J., Mines, M. A., King, M. K., Sweatt, J. D., Miller, C. A., & Jope, R. S. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.09.023 · Cited by 193
The Tyrosine Phosphatase STEP Mediates AMPA Receptor Endocytosis after Metabotropic Glutamate Receptor Stimulation
Zhang, Y., Venkitaramani, D. V., Gladding, C. M., Zhang, Y., Kurup, P. K., Molnár, E., Collingridge, G. L., & Lombroso, P. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2666-08.2008 · Cited by 191
Self-citation
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
Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model
Zhang, Y., Kurup, P. K., Xu, J., Carty, N., Fernandez, S. M., Nygaard, H. B., Pittenger, C., Greengard, P., Strittmatter, S. M., Nairn, A. C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013543107 · Cited by 187
Self-citation
Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420
Nguyen, T.-H., Liu, J., & Lombroso, P. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111683200 · Cited by 185
Self-citation
Developmental and genetic audiogenic seizure models: behavior and biological substrates
Ross, K. C., & Coleman, J. R. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00029-4 · Cited by 181
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
Social behavior deficits in the Fmr1 mutant mouse
Mineur, Y. S., Huynh, L. X., & Crusio, W. E. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.11.004 · Cited by 177
Neuronal networks in the genetically epilepsy-prone rat.
Cl, F. (1999) · PubMed · Cited by 177
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
Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression
Moult, P. R., Gladding, C. M., Sanderson, T. M., Fitzjohn, S. M., Bashir, Z. I., Molnar, E., & Collingridge, G. L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4322-05.2006 · Cited by 172
Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome
Liu, Z., Chuang, D., & Smith, C. B. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000520 · Cited by 168
The fragile X continuum: new advances and perspectives
Cornish, K. M., Turk, J., & Hagerman, R. J. (2008) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2008.01056.x · Cited by 168
Altered Neocortical Rhythmic Activity States inFmr1KO Mice Are Due to Enhanced mGluR5 Signaling and Involve Changes in Excitatory Circuitry
Hays, S. A., Huber, K. M., & Gibson, J. R. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3157-11.2011 · Cited by 163
Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders
Goody, S. M. G., Baum, M. L., Paspalas, C. D., Fernandez, S. M., Carty, N., Kurup, P. K., & Lombroso, P. J. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003053 · Cited by 162
Self-citation
ERK2 Contributes to the Control of Social Behaviors in Mice
Satoh, Y., Endo, S., Nakata, T., Kobayashi, Y., Yamada, K., Ikeda, T., Takeuchi, A., Hiramoto, T., Watanabe, Y., & Kazama, T. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2349-11.2011 · Cited by 145
Differential interaction of the tyrosine phosphatases PTP-SL, STEP and HePTP with the mitogen-activated protein kinases ERK1/2 and p38alpha is determined by a kinase specificity sequence and influenced by reducing agents
MUÑOZ, J. J., TÁRREGA, C., BLANCO-APARICIO, C., & PULIDO, R. (2003) · Biochemical Journal · doi:10.1042/bj20021941 · Cited by 121 · cited 1×
“…of Fyn, Pyk2, ERK1/2 and p38 inactivates these enzymes, whereas dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis (Nguyen et al. 2002; Pelkey et al. 2002; Munoz et al. 2003; Paul et al. 2003; Snyder et al. 2005; Zhang et al. 2008; Venkitaramani et al. 2011).”
Background
The behavioral phenotype of FMR1 mutations
Boyle, L., & Kaufmann, W. E. (2010) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30277 · Cited by 118
Dissociation of social and nonsocial anxiety in a mouse model of fragile X syndrome.
Liu, Z.-H., & Smith, C. B. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.02.066 · Cited by 112
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
Impaired inhibitory control of cortical synchronization in fragile X syndrome
Paluszkiewicz, S. M., Olmos-Serrano, J. L., Corbin, J. G., & Huntsman, M. M. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00421.2011 · Cited by 107
Audiogenic seizures evoked in DBA/2 mice inducec-fos oncogene expression into subcortical auditory nuclei
Salle, G. L. G. L., & Naquet, R. (1990) · Brain Research · doi:10.1016/0006-8993(90)90988-n · Cited by 97
Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome
Kim, S. H., Markham, J. A., Weiler, I. J., & Greenough, W. T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800257105 · Cited by 97
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
Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation
Venkitaramani, D. V., Paul, S., Zhang, Y., Kurup, P. K., Ding, L., Tressler, L., Allen, M. R., Sacca, R. E., Picciotto, M. R., & Lombroso, P. J. (2008) · Synapse · doi:10.1002/syn.20608 · Cited by 90
Self-citation
Molecular and cellular genetics of fragile X syndrome
Kaufmann, W. E., & Reiss, A. L. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990205)88:1 · Cited by 88
STEP61: A Member of a Family of Brain-Enriched PTPs Is Localized to the Endoplasmic Reticulum
Bult, A., Zhao, F., Dirkx, R. A., Sharma, E., Lukácsi, E., Solimena, M., Naegele, J. R., & Lombroso, P. J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-24-07821.1996 · Cited by 83
Self-citation
The greeting behavior of fragile X males.
Wolff, P. H., Gardner, J., Paccla, J., & Lappen, J. (1989) · PubMed · Cited by 77
Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome
Thomas, A. M., Bui, N., Graham, D. F., Perkins, J. R., Yuva‐Paylor, L. A., & Paylor, R. E. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.04.049 · Cited by 74
Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Venkitaramani, D. V., de Moura, P. J., Picciotto, M. R., & Lombroso, P. J. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07687.x · Cited by 68
Self-citation
Neurons in the deep layers of superior colliculus play a critical role in the neuronal network for audiogenic seizures: mechanisms for production of wild running behavior
Faingold, C. L., & Randall, M. E. (1999) · Brain Research · doi:10.1016/s0006-8993(98)01136-6 · Cited by 64
Immunocytochemical localization of the striatal enriched protein tyrosine phosphatase in the rat striatum: A light and electron microscopic study with a complementary DNA-generated polyclonal antibody
Oyama, T., Goto, S., Nishi, T., Sato, K., Yamada, K., Yoshikawa, M., & Ushio, Y. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00278-q · Cited by 60
Effects of harmaline on anxiety-related behavior in mice
Hilber, P., & Chapillon, P. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.07.006 · Cited by 52
A question of balance: a proposal for new mouse models of autism
Murcia, C. L., Gulden, F. O., & Herrup, K. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.07.001 · Cited by 50
The periaqueductal grey is a critical site in the neuronal network for audiogenic seizures: modulation by GABAA, NMDA and opioid receptors
N’Gouemo, P., & Faingold, C. L. (1999) · Epilepsy Research · doi:10.1016/s0920-1211(98)00128-4 · Cited by 47
Unaltered hormonal response to stress in a mouse model of fragile X syndrome
Qin, M., & Smith, C. B. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.03.010 · Cited by 29
STEP regulation of seizure thresholds in the hippocampus
Briggs, S. W., Walker, J., Asik, K., Lombroso, P. J., Naegele, J. R., & Aaron, G. B. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2010.02912.x · Cited by 22
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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
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
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
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
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
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
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
Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test
de Esch, C. E. F., van den Berg, W. E., Buijsen, R. A. M., Jaafar, I. A., Nieuwenhuizen-Bakker, I. M., Gasparini, F., Kushner, S. A., & Willemsen, R. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.12.021 · Cited by 45
Tyrosine phosphatase STEP61 negatively regulates amyloid β‐mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors
Zhang, L., Xie, J., Yang, J., & Cao, Y. (2013) · Journal of Neuroscience Research · doi:10.1002/jnr.23263 · Cited by 28

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
Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium.
(1994) · PubMed · Cited by 565
Chromosome 22q11 deletion syndrome: Update and review of the clinical features, cognitive-behavioral spectrum, and psychiatric complications
Swillen, A., Vogels, A., Devriendt, K., & Fryns, J. P. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(200022)97:2 · Cited by 188
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
Intranuclear inclusions in a fragile X mosaic male
Pretto, D. I., Hunsaker, M. R., Cunningham, C. L., Greco, C., Hagerman, R. J., Noctor, S. C., Hall, D. A., Hagerman, P. J., & Tassone, F. (2013) · Translational Neurodegeneration · doi:10.1186/2047-9158-2-10 · Cited by 40

Authors: Goebel‐Goody, S. M., Wilson‐Wallis, E. D., Royston, S., Tagliatela, S. M., Naegele, J. R., & Lombroso, P. J.
Affiliations: Yale University (US)
Wesleyan University (US)
ORCID: Naegele, J. R.
Venue: Genes, Brain and Behavior
Publisher: Wiley
Published: 2012-04-06
Volume: 11
Issue: 5
Pages: 586-600
ISSN: 1601-183X (ISSN-L)
1601-1848
DOI: 10.1111/j.1601-183x.2012.00781.x
PMC: PMC3922131
OpenAlex: W2000309815
Cited by: 108
References: 89
Citations by year: 2026: 4 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 11 · 2013: 16 · 2012: 4
FWCI: 8.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Genes Brain & Behavior (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (MH 52711, R01MH091037, MH091037, R01MH052711, T32MH018268)
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, STEP, PTPN5, FMRP, Fmr1 knockout mice, metabotropic glutamate receptors, synaptic plasticity, audiogenic seizures, social behavior, anxiety-like behavior, intellectual disability, autism spectrum disorder, Fyn, Pyk2, ERK1/2, p38 MAPK, NMDA receptor, AMPA receptors, periaqueductal gray, c-fos
MeSH terms: Animals, Behavior, Animal, Choice Behavior, Disease Models, Animal, Hippocampus, Motor Activity, Neurons, Social Dominance, Synaptosomes, Proto-Oncogene Proteins c-fos, Receptors, Metabotropic Glutamate, Mice, Knockout, Mice, Fragile X Messenger Ribonucleoprotein 1, Protein Tyrosine Phosphatases, Non-Receptor

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Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model

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