Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.
Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.
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DOI：
10.1523/jneurosci.1161-10.2010
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发表时间：
2010-11-03
期刊：
影响因子：
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通讯作者：
Goldfarb M
中科院分区：
文献类型：
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作者：
Giza J;Urbanski MJ;Prestori F;Bandyopadhyay B;Yam A;Friedrich V;Kelley K;D'Angelo E;Goldfarb M
人类 22q 染色体末端附近 SHANK3 基因的缺失与 Phelan-McDermid 综合征和自闭症谱系障碍有关。几乎所有此类缺失也跨越紧密相连的 IB2 基因。我们在此表明 IB2 蛋白在大脑中广泛表达，并且在突触后密度中高度富集。小鼠 IB2 基因的实验性破坏会减少 AMPA 并增强小脑中 NMDA 受体介导的谷氨酸能传递，改变浦肯野细胞树突乔木的形态，并诱导运动和认知缺陷，表明自闭症表型。这些发现支持人类 IB2 突变作为 Chr22qter 相关认知障碍的遗传因素。
Deletion of the human SHANK3 gene near the terminus of chromosome 22q is associated with Phelan-McDermid syndrome and autism spectrum disorders. Nearly all such deletions also span the tightly linked IB2 gene. We show here that IB2 protein is broadly expressed in the brain and is highly enriched within postsynaptic densities. Experimental disruption of the IB2 gene in mice reduces AMPA and enhances NMDA receptor-mediated glutamatergic transmission in cerebellum, changes the morphology of Purkinje cell dendritic arbors, and induces motor and cognitive deficits suggesting an autism phenotype. These findings support a role for human IB2 mutation as a contributing genetic factor in Chr22qter-associated cognitive disorders.