Cell research · 2016
TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ke Qiong, Li Weiqiang, Lai Xingqiang, Chen Hong, Huang Lihua, Kang Zhuang, Li Kai, Ren Jie, Lin Xiaofeng, Zheng Haiqing, Huang Weijun, Ma Yunhan, Xu Dongdong, Chen Zheng, Song Xinming, Lin Xinyi, Zhuang Min, Wang Tao, Zhuang Fengfeng, Xi Jianzhong, Mao Frank Fuxiang, Xia Huimin, Lahn Bruce T, Zhou Qi, Yang Shihua, Xiang Andy Peng
Аннотация
Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size.