Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
received:
20
10
2023
accepted:
23
09
2024
revised:
14
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
4
10
2024
Statut:
aheadofprint
Résumé
Exome sequencing has enabled the identification of causative genes of monogenic forms of autism, amongst them, in 2016, CSNK2A1, the gene encoding the catalytic subunit of the kinase CK2, linking this kinase to Okur-Chung Neurodevelopmental Syndrome (OCNDS), a newly described neurodevelopmental condition with many symptoms resembling those of autism spectrum disorder. Thus far, no preclinical model of this condition exists. Here we describe a knock-in mouse model that harbors the K198R mutation in the activation segment of the α subunit of CK2. This region is a mutational hotspot, representing one-third of patients. These mice exhibit behavioral phenotypes that mirror patient symptoms. Homozygous knock-in mice die mid-gestation while heterozygous knock-in mice are born at half of the expected mendelian ratio and are smaller in weight and size than wildtype littermates. Heterozygous knock-in mice showed alterations in cognition and memory-assessing paradigms, enhanced stereotypies, altered circadian activity patterns, and nesting behavior. Phosphoproteome analysis from brain tissue revealed alterations in the phosphorylation status of major pre- and postsynaptic proteins of heterozygous knock-in mice. In congruence, we detect reduced synaptic maturation in hippocampal neurons and attenuated long-term potentiation in the hippocampus of knock-in mice. Taken together, heterozygous knock-in mice (CK2α
Identifiants
pubmed: 39367055
doi: 10.1038/s41380-024-02762-8
pii: 10.1038/s41380-024-02762-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 894207
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Frances L, Quintero J, Fernandez A, Ruiz A, Caules J, Fillon G, et al. Current state of knowledge on the prevalence of neurodevelopmental disorders in childhood according to the DSM-5: a systematic review in accordance with the PRISMA criteria. Child Adolesc Psychiatry Ment Health. 2022;16:27.
pubmed: 35361232
pmcid: 8973738
doi: 10.1186/s13034-022-00462-1
Parenti I, Rabaneda LG, Schoen H, Novarino G. Neurodevelopmental disorders: from genetics to functional pathways. Trends Neurosci. 2020;43:608–21.
pubmed: 32507511
doi: 10.1016/j.tins.2020.05.004
Baron-Cohen S, Belmonte MK. Autism: a window onto the development of the social and the analytic brain. Annu Rev Neurosci. 2005;28:109–26.
pubmed: 16033325
doi: 10.1146/annurev.neuro.27.070203.144137
Okur V, Cho MT, Henderson L, Retterer K, Schneider M, Sattler S, et al. De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features. Hum Genet. 2016;135:699–705.
pubmed: 27048600
doi: 10.1007/s00439-016-1661-y
Trinh J, Huning I, Budler N, Hingst V, Lohmann K, Gillessen-Kaesbach G. A novel de novo mutation in CSNK2A1: reinforcing the link to neurodevelopmental abnormalities and dysmorphic features. J Hum Genet. 2017;62:1005–6.
pubmed: 28725024
doi: 10.1038/jhg.2017.73
Chiu ATG, Pei SLC, Mak CCY, Leung GKC, Yu MHC, Lee SL, et al. Okur-Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion. Clin Genet. 2018;93:880–90.
pubmed: 29240241
doi: 10.1111/cge.13196
Owen CI, Bowden R, Parker MJ, Patterson J, Patterson J, Price S, et al. Extending the phenotype associated with the CSNK2A1-related Okur-Chung syndrome-A clinical study of 11 individuals. Am J Med Genet A. 2018;176:1108–14.
Colavito D, Del Giudice E, Ceccato C, Dalle Carbonare M, Leon A, Suppiej A. Are CSNK2A1 gene mutations associated with retinal dystrophy? Report of a patient carrier of a novel de novo splice site mutation. J Hum Genet. 2018;63:779–81.
pubmed: 29568000
doi: 10.1038/s10038-018-0434-y
Akahira-Azuma M, Tsurusaki Y, Enomoto Y, Mitsui J, Kurosawa K. Refining the clinical phenotype of Okur-Chung neurodevelopmental syndrome. Hum Genome Var. 2018;5:18011.
pubmed: 29619237
pmcid: 5874396
doi: 10.1038/hgv.2018.11
Martinez-Monseny AF, Casas-Alba D, Arjona C, Bolasell M, Casano P, Muchart J, et al. Okur-Chung neurodevelopmental syndrome in a patient from Spain. Am J Med Genet A. 2020;182:20–4.
pubmed: 31729156
doi: 10.1002/ajmg.a.61405
Wu RH, Tang WT, Qiu KY, Li XJ, Tang DX, Meng Z, et al. Identification of novel CSNK2A1 variants and the genotype-phenotype relationship in patients with Okur-Chung neurodevelopmental syndrome: a case report and systematic literature review. J Int Med Res. 2021;49:3000605211017063.
pubmed: 34038195
doi: 10.1177/03000605211017063
Ceglia I, Flajolet M, Rebholz H. Predominance of CK2alpha over CK2alpha’ in the mammalian brain. Mol Cell Biochem. 2011;356:169–75.
pubmed: 21761202
doi: 10.1007/s11010-011-0963-6
Niefind K, Guerra B, Ermakowa I, Issinger OG. Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme. EMBO J. 2001;20:5320–31.
pubmed: 11574463
doi: 10.1093/emboj/20.19.5320
Ruzzene M, Pinna LA. Addiction to protein kinase CK2: a common denominator of diverse cancer cells? Biochim Biophys Acta. 2010;1804:499–504.
pubmed: 19665589
doi: 10.1016/j.bbapap.2009.07.018
D’Amore C, Borgo C, Sarno S, Salvi M. Role of CK2 inhibitor CX-4945 in anti-cancer combination therapy - potential clinical relevance. Cell Oncol. 2020;43:1003–16.
doi: 10.1007/s13402-020-00566-w
Girault JA, Hemmings HC Jr, Zorn SH, Gustafson EL, Greengard P. Characterization in mammalian brain of a DARPP-32 serine kinase identical to casein kinase II. J Neurochem. 1990;55:1772–83.
pubmed: 2145398
doi: 10.1111/j.1471-4159.1990.tb04968.x
Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O’Brien C, Seldin DC. The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Mol Cell Biol. 2008;28:131–9.
pubmed: 17954558
doi: 10.1128/MCB.01119-07
Rebholz H, Nishi A, Liebscher S, Nairn AC, Flajolet M, Greengard P. CK2 negatively regulates Galphas signaling. Proc Natl Acad Sci USA. 2009;106:14096–101.
pubmed: 19666609
doi: 10.1073/pnas.0906857106
Castello J, LeFrancois B, Flajolet M, Greengard P, Friedman E, Rebholz H. CK2 regulates 5-HT4 receptor signaling and modulates depressive-like behavior. Mol Psychiatry. 2017;23:872–82.
Rebholz H, Zhou M, Nairn AC, Greengard P, Flajolet M. Selective knockout of the casein kinase 2 in d1 medium spiny neurons controls dopaminergic function. Biol Psychiatry. 2013;74:113–21.
pubmed: 23290496
doi: 10.1016/j.biopsych.2012.11.013
Dominguez I, Cruz-Gamero JM, Corasolla V, Dacher N, Rangasamy S, Urbani A, et al. Okur-Chung neurodevelopmental syndrome-linked CK2alpha variants have reduced kinase activity. Hum Genet. 2021;140:1077–96.
pubmed: 33944995
doi: 10.1007/s00439-021-02280-5
Werner C, Gast A, Lindenblatt D, Nickelsen A, Niefind K, Jose J, et al. Structural and enzymological evidence for an altered substrate specificity in Okur-Chung Neurodevelopmental Syndrome Mutant CK2alpha(Lys198Arg). Front Mol Biosci. 2022;9:831693.
pubmed: 35445078
doi: 10.3389/fmolb.2022.831693
Caefer DM, Phan NQ, Liddle JC, Balsbaugh JL, O’Shea JP, Tzingounis AV, et al. The Okur-Chung Neurodevelopmental Syndrome Mutation CK2(K198R) Leads to a Rewiring of Kinase Specificity. Front Mol Biosci. 2022;9:850661.
pubmed: 35517865
doi: 10.3389/fmolb.2022.850661
Ballardin D, Cruz-Gamero JM, Bienvenu T, Rebholz H. Comparing two neurodevelopmental disorders linked to CK2: Okur-Chung neurodevelopmental syndrome and Poirier-Bienvenu neurodevelopmental syndrome-two sides of the same coin? Front Mol Biosci. 2022;9:850559.
pubmed: 35693553
doi: 10.3389/fmolb.2022.850559
Dodero L, Damiano M, Galbusera A, Bifone A, Tsaftsaris SA, Scattoni ML, et al. Neuroimaging evidence of major morpho-anatomical and functional abnormalities in the BTBR T+TF/J mouse model of autism. PLoS ONE. 2013;8:e76655.
pubmed: 24146902
doi: 10.1371/journal.pone.0076655
Wolff JJ, Gerig G, Lewis JD, Soda T, Styner MA, Vachet C, et al. Altered corpus callosum morphology associated with autism over the first 2 years of life. Brain. 2015;138:2046–58.
pubmed: 25937563
pmcid: 4492413
doi: 10.1093/brain/awv118
Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, et al. Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ. 2005;12:668–77.
pubmed: 15818404
doi: 10.1038/sj.cdd.4401604
Gazestani VH, Pramparo T, Nalabolu S, Kellman BP, Murray S, Lopez L, et al. A perturbed gene network containing PI3K-AKT, RAS-ERK and WNT-beta-catenin pathways in leukocytes is linked to ASD genetics and symptom severity. Nat Neurosci. 2019;22:1624–34.
pubmed: 31551593
doi: 10.1038/s41593-019-0489-x
Bibby AC, Litchfield DW. The multiple personalities of the regulatory subunit of protein kinase CK2: CK2 dependent and CK2 independent roles reveal a secret identity for CK2beta. Int J Biol Sci. 2005;1:67–79.
pubmed: 15951851
doi: 10.7150/ijbs.1.67
Fenster SD, Chung WJ, Zhai R, Cases-Langhoff C, Voss B, Garner AM, et al. Piccolo, a presynaptic zinc finger protein structurally related to bassoon. Neuron. 2000;25:203–14.
pubmed: 10707984
doi: 10.1016/S0896-6273(00)80883-1
Meggio F, Marin O, Pinna LA. Substrate specificity of protein kinase CK2. Cell Mol Biol Res. 1994;40:401–9.
pubmed: 7735314
Schumann CM, Hamstra J, Goodlin-Jones BL, Lotspeich LJ, Kwon H, Buonocore MH, et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24:6392–401.
pubmed: 15254095
pmcid: 6729537
doi: 10.1523/JNEUROSCI.1297-04.2004
Banker SM, Gu X, Schiller D, Foss-Feig JH. Hippocampal contributions to social and cognitive deficits in autism spectrum disorder. Trends Neurosci. 2021;44:793–807.
pubmed: 34521563
pmcid: 8484056
doi: 10.1016/j.tins.2021.08.005
Kouser M, Speed HE, Dewey CM, Reimers JM, Widman AJ, Gupta N, et al. Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission. J Neurosci. 2013;33:18448–68.
pubmed: 24259569
pmcid: 3834052
doi: 10.1523/JNEUROSCI.3017-13.2013
Ravizza SM, Solomon M, Ivry RB, Carter CS. Restricted and repetitive behaviors in autism spectrum disorders: the relationship of attention and motor deficits. Dev Psychopathol. 2013;25:773–84.
pubmed: 23880391
pmcid: 5538881
doi: 10.1017/S0954579413000163
Courchet V, Roberts AJ, Meyer-Dilhet G, Del Carmine P, Lewis TL Jr, Polleux F, et al. Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice. Nat Commun. 2018;9:4289.
pubmed: 30327473
pmcid: 6191442
doi: 10.1038/s41467-018-06584-5
Turner AH, Greenspan KS, van Erp TGM. Pallidum and lateral ventricle volume enlargement in autism spectrum disorder. Psychiatry Res Neuroimaging. 2016;252:40–5.
pubmed: 27179315
pmcid: 5920514
doi: 10.1016/j.pscychresns.2016.04.003
Movsas TZ, Pinto-Martin JA, Whitaker AH, Feldman JF, Lorenz JM, Korzeniewski SJ, et al. Autism spectrum disorder is associated with ventricular enlargement in a low birth weight population. J Pediatr. 2013;163:73–8.
pubmed: 23410601
pmcid: 4122247
doi: 10.1016/j.jpeds.2012.12.084
Egaas B, Courchesne E, Saitoh O. Reduced size of corpus callosum in autism. Arch Neurol. 1995;52:794–801.
pubmed: 7639631
doi: 10.1001/archneur.1995.00540320070014
Chiu ATG, Pei SLC, Mak CCY, Leung GKC, Yu MHC, Lee SL, et al. Okur‐Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion. Clin Genet. 2018;93:880–90.
pubmed: 29240241
doi: 10.1111/cge.13196
Wu R, Tang W, Qiu K, Li X, Tang D, Meng Z, et al. Identification of novel CSNK2A1 variants and the genotype–phenotype relationship in patients with Okur–Chung neurodevelopmental syndrome: a case report and systematic literature review. J Int Med Res. 2021;49:030006052110170.
Girault JA, Hemmings HC Jr, Williams KR, Nairn AC, Greengard P. Phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by casein kinase II. J Biol Chem. 1989;264:21748–59.
pubmed: 2557337
doi: 10.1016/S0021-9258(20)88248-9
Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn JH, Maroteaux M, et al. A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature. 2008;453:879–84.
pubmed: 18496528
pmcid: 2796210
doi: 10.1038/nature06994
Huber KM, Klann E, Costa-Mattioli M, Zukin RS. Dysregulation of mammalian target of Rapamycin signaling in mouse models of autism. J Neurosci. 2015;35:13836–42.
pubmed: 26468183
pmcid: 4604222
doi: 10.1523/JNEUROSCI.2656-15.2015
Chen J, Alberts I, Li X. Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders. Int J Dev Neurosci. 2014;35:35–41.
pubmed: 24662006
doi: 10.1016/j.ijdevneu.2014.03.006
Yeung KS, Tso WWY, Ip JJK, Mak CCY, Leung GKC, Tsang MHY, et al. Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism. Mol Autism. 2017;8:66.
pubmed: 29296277
pmcid: 5738835
doi: 10.1186/s13229-017-0182-4
Mencer S, Kartawy M, Lendenfeld F, Soluh H, Tripathi MK, Khaliulin I, et al. Proteomics of autism and Alzheimer’s mouse models reveal common alterations in mTOR signaling pathway. Transl Psychiatry. 2021;11:480.
pubmed: 34535637
pmcid: 8448888
doi: 10.1038/s41398-021-01578-2
Ding X, Bloch W, Iden S, Ruegg MA, Hall MN, Leptin M, et al. mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation. Nat Commun. 2016;7:13226.
pubmed: 27807348
pmcid: 5095294
doi: 10.1038/ncomms13226
Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci. 2008;28:5422–32.
pubmed: 18495876
pmcid: 2633923
doi: 10.1523/JNEUROSCI.0955-08.2008
Franchin C, Borgo C, Cesaro L, Zaramella S, Vilardell J, Salvi M, et al. Re-evaluation of protein kinase CK2 pleiotropy: new insights provided by a phosphoproteomics analysis of CK2 knockout cells. Cell Mol Life Sci. 2018;75:2011–26.
pubmed: 29119230
doi: 10.1007/s00018-017-2705-8
Huguet GEE, Bourgeron T. The genetic landscapes of autism spectrum disorders. T. Annu Rev Genomics Hum Genet. 2013;14:191–213.
pubmed: 23875794
doi: 10.1146/annurev-genom-091212-153431
Chung HJ, Huang YH, Lau LF, Huganir RL. Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand. J Neurosci. 2004;24:10248–59.
pubmed: 15537897
doi: 10.1523/JNEUROSCI.0546-04.2004
Bulat V, Rast M, Pielage J. Presynaptic CK2 promotes synapse organization and stability by targeting Ankyrin2. J Cell Biol. 2014;204:77–94.
pubmed: 24395637
doi: 10.1083/jcb.201305134
Kimura R, Matsuki N. Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampus. J Physiol. 2008;586:3195–206.
pubmed: 18483072
doi: 10.1113/jphysiol.2008.151894
Kraeuter AK, Guest PC, Sarnyai Z. The Y-Maze for assessment of spatial working and reference memory in mice. Methods Mol Biol. 2019;1916:105–11.
pubmed: 30535688
doi: 10.1007/978-1-4939-8994-2_10
Zhang CL, Aime M, Laheranne E, Houbaert X, El Oussini H, Martin C, et al. Protein Kinase A deregulation in the medial prefrontal cortex impairs working memory in Murine Oligophrenin-1 deficiency. J Neurosci. 2017;37:11114–26.
pubmed: 29030432
doi: 10.1523/JNEUROSCI.0351-17.2017
Porcu M, Cocco L, Marrosu F, Cau R, Suri JS, Qi Y, et al. Impact of corpus callosum integrity on functional interhemispheric connectivity and cognition in healthy subjects. Brain Imaging Behav. 2024;18:141–58.
pubmed: 37955809
doi: 10.1007/s11682-023-00814-1
Frederiksen KS. Corpus callosum in aging and dementia. Dan Med J. 2013;60:B4721.
pubmed: 24083533
Negron-Oyarzo I, Neira D, Espinosa N, Fuentealba P, Aboitiz F. Prenatal stress produces persistence of remote memory and disrupts functional connectivity in the Hippocampal-Prefrontal Cortex Axis. Cereb Cortex. 2015;25:3132–43.
pubmed: 24860018
doi: 10.1093/cercor/bhu108
Rodriguez GA, Burns MP, Weeber EJ, Rebeck GW. Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex. Learn Mem. 2013;20:256–66.
pubmed: 23592036
doi: 10.1101/lm.030031.112
Gawel K, Gibula E, Marszalek-Grabska M, Filarowska J, Kotlinska JH. Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration. Naunyn Schmiedebergs Arch Pharmacol. 2019;392:1–18.
pubmed: 30470917
doi: 10.1007/s00210-018-1589-y
Kim JJ, Diamond DM. The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci. 2002;3:453–62.
pubmed: 12042880
doi: 10.1038/nrn849
Rohleder C, Wiedermann D, Neumaier B, Drzezga A, Timmermann L, Graf R, et al. The functional networks of prepulse inhibition: neuronal connectivity analysis based on FDG-PET in awake and unrestrained rats. Front Behav Neurosci. 2016;10:148.
pubmed: 27493627
doi: 10.3389/fnbeh.2016.00148
Kedia S, Chattarji S. Marble burying as a test of the delayed anxiogenic effects of acute immobilisation stress in mice. J Neurosci Methods. 2014;233:150–4.
pubmed: 24932962
doi: 10.1016/j.jneumeth.2014.06.012
Moy SS, Riddick NV, Nikolova VD, Teng BL, Agster KL, Nonneman RJ, et al. Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism. Behav Brain Res. 2014;259:200–14.
pubmed: 24211371
doi: 10.1016/j.bbr.2013.10.052
Sungur AO, Vorckel KJ, Schwarting RK, Wohr M. Repetitive behaviors in the Shank1 knockout mouse model for autism spectrum disorder: developmental aspects and effects of social context. J Neurosci Methods. 2014;234:92–100.
pubmed: 24820912
doi: 10.1016/j.jneumeth.2014.05.003
Sonzogni M, Wallaard I, Santos SS, Kingma J, du Mee D, van Woerden GM, et al. A behavioral test battery for mouse models of Angelman syndrome: a powerful tool for testing drugs and novel Ube3a mutants. Mol Autism. 2018;9:47.
pubmed: 30220990
doi: 10.1186/s13229-018-0231-7
Amodeo DA, Jones JH, Sweeney JA, Ragozzino ME. Differences in BTBR T+ tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors. Behav Brain Res. 2012;227:64–72.
pubmed: 22056750
doi: 10.1016/j.bbr.2011.10.032
Shmelkov SV, Hormigo A, Jing D, Proenca CC, Bath KG, Milde T, et al. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010;16:598–602.
pubmed: 20418887
doi: 10.1038/nm.2125
Spencer CM, Alekseyenko O, Hamilton SM, Thomas AM, Serysheva E, Yuva-Paylor LA, et al. Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses. Autism Res. 2011;4:40–56.
pubmed: 21268289
pmcid: 3059810
doi: 10.1002/aur.168
Balaan C, Corley MJ, Eulalio T, Leite-Ahyo K, Pang APS, Fang R, et al. Juvenile Shank3b deficient mice present with behavioral phenotype relevant to autism spectrum disorder. Behav Brain Res. 2019;356:137–47.
pubmed: 30134148
doi: 10.1016/j.bbr.2018.08.005
Blundell J, Blaiss CA, Etherton MR, Espinosa F, Tabuchi K, Walz C, et al. Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. J Neurosci. 2010;30:2115–29.
pubmed: 20147539
pmcid: 2824441
doi: 10.1523/JNEUROSCI.4517-09.2010
Han KA, Yoon TH, Shin J, Um JW, Ko J. Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice. Mol Autism. 2020;11:87.
pubmed: 33126897
pmcid: 7602353
doi: 10.1186/s13229-020-00392-9
Silverman JL, Turner SM, Barkan CL, Tolu SS, Saxena R, Hung AY, et al. Sociability and motor functions in Shank1 mutant mice. Brain Res. 2011;1380:120–37.
pubmed: 20868654
doi: 10.1016/j.brainres.2010.09.026