Intersectin 1对体内表型有影响：对唐氏综合征的意义。
Intersectin 1 contributes to phenotypes in vivo: implications for Down's syndrome.
作者信息
Hunter Michael P, Nelson Marianela, Kurzer Michael, Wang Xuerong, Kryscio Richard J, Head Elizabeth, Pinna Graziano, O'Bryan John P
机构信息
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
出版信息
Neuroreport. 2011 Oct 26;22(15):767-72. doi: 10.1097/WNR.0b013e32834ae348.
Abstract
Intersectin 1 (ITSN1) is a human chromosome 21 (HSA21) gene product encoding a multidomain scaffold protein that functions in endocytosis, signal transduction, and is implicated in Down's syndrome, Alzheimer's Disease, and potentially other neurodegenerative diseases through activation of c-Jun N-terminal kinase. We report for the first time that ITSN1 proteins are elevated in individuals with Down's syndrome of varying ages. However, ITSN1 levels decreased in aged cases with Down's syndrome with Alzheimer's disease-like neuropathology. Analysis of a novel ITSN1 transgenic mouse reveals that ITSN1 overexpression results in a sex-dependent decrease in locomotor activity. This study reveals a link between overexpression of specific ITSN1 isoforms and behavioral phenotypes and has implications for human neurodegenerative diseases such as Down's syndrome and Alzheimer's disease.
摘要
交叉蛋白1（ITSN1）是一种人类21号染色体（HSA21）基因产物，编码一种多结构域支架蛋白，该蛋白在内吞作用、信号转导中发挥作用，并通过激活c-Jun氨基末端激酶与唐氏综合征、阿尔茨海默病以及其他潜在的神经退行性疾病有关。我们首次报告，不同年龄的唐氏综合征患者体内ITSN1蛋白水平升高。然而，患有类似阿尔茨海默病神经病理学的老年唐氏综合征患者体内ITSN1水平下降。对一种新型ITSN1转基因小鼠的分析表明，ITSN1过表达导致运动活性出现性别依赖性降低。这项研究揭示了特定ITSN1亚型的过表达与行为表型之间的联系，并对唐氏综合征和阿尔茨海默病等人类神经退行性疾病具有启示意义。
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