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Cell Res:中山大学柯琼研究员发表基因编辑研究论文

摘要 : 近日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表了中山大学中山医学院柯琼博士题为“TALEN-based generation of a cynomolgus monkey disease model for human microcephaly”的研究论文。

 近日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表了中山大学中山医学院柯琼博士题为“TALEN-based generation of a cynomolgus monkey disease model for human microcephaly”的研究论文。

灵长类动物具有与人类相似的解剖结构和生理生化表现,在神经系统发育、认知和行为学等方面的研究中具有啮齿类动物不可比拟的优势,是研究人类疾病特别是神经系统相关疾病的重要工具。随着基因编辑技术的迅速发展,快速获得基因敲除灵长类动物模型成为可能。

柯琼博士在该文章中,报道了利用TALEN技术建立了人类小头畸形相关基因(MCPH1)突变的食蟹猴模型,表现为小头畸形、胼胝体发育不良及上肢痉挛等重要的人类小头症症状,首次证实利用该技术可获得具有人类神经系统相关疾病表型的灵长类动物模型。

目前,柯琼博士在干细胞与组织工程教育部重点实验室负责人类疾病灵长类动物模型研究平台的工作,利用TALEN及CRISPR/CAS9基因编辑技术已获得FAH(酪氨酸血症I型)、SHANK3(自闭症)等基因敲除的食蟹猴模型,为进一步深入研究相关疾病的发病机制,探讨利用干细胞进行修复或器官替代奠定了基础。

原文链接:

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

原文摘要:

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 MCPH1mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelicMCPH1 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.

来源: Cell Research 浏览次数:0

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