Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis.
Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis.
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DOI：
10.1007/s00335-012-9391-5
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发表时间：
2012-06
期刊：
影响因子：
2.5
通讯作者：
Paylor, Richard
中科院分区：
文献类型：
--
作者：
Cowin, Randi-Michelle;Nghiem Bui;Graham, Deanna;Green, Jennie R.;Yuva-Paylor, Lisa A.;Weiss, Andreas;Paylor, Richard
亨廷顿病(HD)症状的变异和改变在患者群体和动物模型中都很常见。利用R6/2 HD小鼠模型的稳定系，本研究调查了遗传背景在转基因小鼠HD症状的发生和严重程度中的作用。对R6/2同源基因C57BL/6J和C57BL/6J×DBA/2J F1(B6D2F1)小鼠的存活率和一些行为表型进行了评估。本研究报告了DBA/2J等位基因的存在导致了R6/2小鼠模型特有的几种HD样表型的改善或恶化，并表明存在HD症状的显性遗传修饰者。这项研究是识别导致自然遗传变异和改变HD症状的基因的第一步。这一鉴定可能导致新的治疗靶点，并有助于阐明HD发病的分子机制。
Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HD mouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenic mouse. R6/2 congenic C57BL/6J and C57BL/6J × DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis.
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影响因子：
30.8
作者：
ANDREW, SE;GOLDBERG, YP;HAYDEN, MR
通讯作者：
HAYDEN, MR
影响因子：
3.7
作者：
Cowin, Randi-Michelle;Bui, Nghiem;Paylor, Richard
通讯作者：
Paylor, Richard
影响因子：
30.8
作者：
SNELL, RG;MACMILLAN, JC;SHAW, DJ
通讯作者：
SHAW, DJ
影响因子：
30.8
作者：
DUYAO, M;AMBROSE, C;MACDONALD, M
通讯作者：
MACDONALD, M
影响因子：
2.2
作者：
Metzger, S;Bauer, P;Riess, O
通讯作者：
Riess, O