Ha, Seungmin Lee, Dongwon Cho, Yi Sul Chung, Changuk Yoo, Ye-Eun Kim, Jihye Lee, Jiseok Kim, Woohyun Kim, Hyosang Bae, Yong Chul Tanaka-Yamamoto, Keiko Kim, Eunjoon 2024-01-20T03:00:57Z 2024-01-20T03:00:57Z 2021-09-05 2016-11-30 0270-6474 https://pubs.kist.re.kr/handle/201004/123412 Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre; Shank2(fl/fl) mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre; Shank2(fl/fl) mice do not recapitulate autistic-like behaviors observed in Shank2(-/-) mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre; Shank2(fl/fl) mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shan2(-/-) mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. English SOC NEUROSCIENCE GLUTAMATE-RECEPTOR DELTA-2 AUTISTIC-LIKE BEHAVIORS POSTSYNAPTIC DENSITY MICE LACKING MUTANT MICE DIFFERENTIAL EXPRESSION BINDING-PROTEIN EMERGING ROLE FAMILY DOMAIN Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors Article 10.1523/JNEUROSCI.1849-16.2016 1 JOURNAL OF NEUROSCIENCE, v.36, no.48, pp.12129 - 12143 JOURNAL OF NEUROSCIENCE 36 48 12129 12143 scie scopus 000391140400007 2-s2.0-85006022092 Neurosciences Neurosciences & Neurology Article GLUTAMATE-RECEPTOR DELTA-2 AUTISTIC-LIKE BEHAVIORS POSTSYNAPTIC DENSITY MICE LACKING MUTANT MICE DIFFERENTIAL EXPRESSION BINDING-PROTEIN EMERGING ROLE FAMILY DOMAIN autism cerebellum excitatory synapse GluD2 Purkinje cell Shank2