目的 研究肥胖主效基因SH2B1与孤独症谱系障碍(ASD)认知和社交功能的关联,为ASD病因学研究提供思路。方法 应用动物行为学实验和转录组测序技术,比较BTBR小鼠(n=6)与对照小鼠(n=6)认知、社交水平差异及SH2B1基因表达水平的差异。构建SH2B1基因敲除小鼠(SH2B1-/-小鼠)(n=6),比较其与对照小鼠之间认知水平及社交功能的差异,并使用Western-Blot实验探究SH2B1-/-小鼠海马组织中认知相关蛋白磷酸化水平的改变。结果 BTBR小鼠较对照小鼠认知水平显著降低(P<0.05),社交能力显著下降(P<0.05),SH2B1基因表达水平下调(P<0.05)。SH2B1-/-小鼠较对照小鼠表现出认知水平降低(P<0.05)以及社交功能损害(P<0.05)。SH2B1-/-小鼠认知相关蛋白CREB和CaMKⅡ磷酸化水平低于对照组小鼠,差异有统计学意义(t=2.74、3.62,P<0.05)。结论 SH2B1基因可能与ASD认知和社交功能损伤高度相关。
Abstract
Objective To discuss the association between the obesity major gene SH2B1 and the cognitive and social functions of autism spectrum disorder(ASD),so as to provide ideas for the etiology of ASD. Methods Using animal behavior tests and RNA-seq,the differences in cognitive and social level and SH2B1 gene expression levels between BTBR mice(n=6)and control mice(n=6)were compared.SH2B1 knockout mice(SH2B1-/- mice)(n=6)were constructed,then the differences in cognitive level and social function between them and control mice were compared.Western-blot experiment was used to explore the changes in the phosphorylation level of cognitive-related proteins in the hippocampus of SH2B1-/- mice. Results Compared with control mice,BTBR mice had lower cognitive level(P<0.05),lower social skills(P<0.05),and down-regulation of SH2B1 gene expression level(P<0.05).Compared with control mice,SH2B1-/- mice showed lower cognitive level(P<0.05)and impairment of social function(P<0.05).Cognitive-related proteins CREB and CaMKⅡ phosphorylation levels of SH2B1-/- mice were significantly reduced than those in control group(t=2.74,3.62,P<0.01). Conclusion The SH2B1 gene may be highly related to the impairment of cognitive and social functions of ASD.
关键词
孤独症谱系障碍 /
SH2B1 /
认知 /
认知相关蛋白 /
社交障碍
Key words
autism spectrum disorder /
SH2B1 /
cognition /
cognition-related proteins /
social disability
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