肥胖主效基因SH2B1与孤独症谱系障碍认知社交功能的关联研究

doi:10.11852/zgetbjzz2021-0439

中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (9): 960-964.DOI: 10.11852/zgetbjzz2021-0439

肥胖主效基因SH2B1与孤独症谱系障碍认知社交功能的关联研究

李晨蕊¹, 李齐¹, 张延承², 李想¹, 于迪¹, 石雅馨¹, 范莉莉¹, 武丽杰¹

1.哈尔滨医科大学公共卫生学院儿少卫生与妇幼保健学教研室,黑龙江哈尔滨 150081;
2.哈尔滨市第一专科医院

收稿日期:2021-03-25 修回日期:2021-05-06 发布日期:2021-09-07 出版日期:2021-09-10
通讯作者: 武丽杰,E-mail:wulijiehyd@126.com
作者简介:李晨蕊(1994-),女,山西人,硕士在读,主要研究方向为儿童发育障碍及行为问题。
基金资助:
国家自然科学基金(8187120715)

Association of obesity major gene SH2B1 with cognitive and social functions of autism spectrum disorder

LI Chen-rui^*, LI Qi, ZHANG Yan-cheng, LI Xiang, YU Di, SHI Ya-xin, FAN Li-li, WU Li-jie

^*Department of Children's and Adolescent Health,Public Health College,Harbin Medical University, Harbin,Heilongjiang 150081,China

Received:2021-03-25 Revised:2021-05-06 Online:2021-09-10 Published:2021-09-07
Contact: WU Li-jie,E-mail:wulijiehyd@126.com

摘要/Abstract

摘要： 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。

关键词: 孤独症谱系障碍, SH2B1, 认知, 认知相关蛋白, 社交障碍

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.

Key words: autism spectrum disorder, SH2B1, cognition, cognition-related proteins, social disability

中图分类号:

R749.94

李晨蕊, 李齐, 张延承, 李想, 于迪, 石雅馨, 范莉莉, 武丽杰. 肥胖主效基因SH2B1与孤独症谱系障碍认知社交功能的关联研究[J]. 中国儿童保健杂志, 2021, 29(9): 960-964.

LI Chen-rui, LI Qi, ZHANG Yan-cheng, LI Xiang, YU Di, SHI Ya-xin, FAN Li-li, WU Li-jie. Association of obesity major gene SH2B1 with cognitive and social functions of autism spectrum disorder[J]. Chinese Journal of Child Health Care, 2021, 29(9): 960-964.

参考文献

[1] International Journal of Psychiatry and Neurology American Psychiatric Association DSM-Task Force Arlington VA US.Diagnostic and statistical manual of mental disorders:DSM-5(5th ed.)[J].Codas,2013,25(2):191.
[2] Zheng Z,Zhang L,Li S,et al.Association among obesity,overweight and autism spectrum disorder:a systematic review and meta-analysis[J].Sci Rep,2017,7(1):11697.
[3] Curtin C,Anderson SE,Must A,et al.The prevalence of obesity in children with autism:a secondary data analysis using nationally representative data from the National Survey of Children's Health[J].BMC Pediatr,2010,10:11.
[4] Criado KK,Sharp WG,McCracken CE,et al.Overweight and obese status in children with autism spectrum disorder and disruptive behavior[J].Autism,2018,22(4):450-459.
[5] Chen AY,Kim SE,Houtrow AJ,et al.Prevalence of obesity among children with chronic conditions[J].Obesity(Silver Spring),2010,18(1):210-213.
[6] 李阳,梁爽,韩盼盼,等.孤独症谱系障碍儿童体成分病例对照研究[J].中国学校卫生,2016,37(6):831-834.
[7] Ren D,Zhou Y,Morris D,et al.Neuronal SH2B1 is essential for controlling energy and glucose homeostasis[J].J Clin Invest,2007,117(2):397-406.
[8] Doche ME,Bochukova EG,Su HW,et al.Human SH2B1 mutations are associated with maladaptive behaviors and obesity[J].J Clin Invest,2012,122(12):4732-4736.
[9] Jiang L,Su H,Keogh JM,et al.Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression[J].Faseb J,2018,32(4):1830-1840.
[10] Liang S,Li Z,Wang Y,et al.Genome-wide DNA methylation analysis reveals epigenetic pattern of in Chinese monozygotic twins discordant for autism spectrum disorder[J].Front Neurosci,2019,13:712.
[11] Maenner MJ,Shaw KA,Baio J,et al.Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network,11 sites,United States,2016[J].MMWR Surveill Summ,2020,69(4):1-12.
[12] Bachmann-Gagescu R,Mefford HC,Cowan C,et al.Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity[J].Genet Med,2010,12(10):641-647.
[13] Morris DL,Rui L.Recent advances in understanding leptin signaling and leptin resistance[J].Am J Physiol Endocrinol Metab,2009,297(6):e1247-e1259.
[14] Selvanayagam T,Walker S,Gazzellone MJ,et al.Genome-wide copy number variation analysis identifies novel candidate loci associated with pediatric obesity[J].Eur J Hum Genet,2018,26(11):1588-1596.
[15] Tabet AC,Pilorge M,Delorme R,et al.Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother[J].Eur J Hum Genet,2012,20(5):540-546.
[16] Yap CX,Alvares GA,Henders AK,et al.Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank[J].Mol Autism,2021,12(1):12.
[17] Meyza KZ,Defensor EB,Jensen AL,et al.The BTBR T+tf/J mouse model for autism spectrum disorders-in search of biomarkers[J].Behav Brain Res,2013,251:25-34.
[18] Kida S,Josselyn SA,Peña de Ortiz S,et al.CREB required for the stability of new and reactivated fear memories[J].Nat Neurosci,2002,5(4):348-355.
[19] Rossetti T,Banerjee S,Kim C,et al.Memory erasure experiments indicate a critical role of CaMKII in memory storage[J].Neuron,2017,96(1):207-216.

肥胖主效基因SH2B1与孤独症谱系障碍认知社交功能的关联研究

Association of obesity major gene SH2B1 with cognitive and social functions of autism spectrum disorder

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