唐氏综合征的非嵌合易位型跨染色体鼠模型，携带人类 21 号染色体的长臂。
A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21.
机构信息
Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Japan.
Chromosome Engineering Research Center (CERC), Tottori University, Yonago, Japan.
出版信息
Elife. 2020 Jun 29;9:e56223. doi: 10.7554/eLife.56223.
Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we "clone" the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc(HSA21q;MAC)1Yakaz ("TcMAC21"). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.
唐氏综合征（DS）动物模型，即人类 21 号染色体（HSA21）基因或同源基因的三体，为深入了解和治疗方案提供了线索。唯一现有的易位（Tc）DS 模型 Tc1 携带了一个 HSA21，其中超过 50 个蛋白编码基因（PCGs）被破坏。Tc1 是嵌合体，影响结果的解释。在这里，我们将 HSA21 的 34MB 长臂（HSA21q）“克隆”为小鼠人工染色体（MAC）。通过多次微细胞介导的染色体转移步骤，我们创建了一个新的 Tc DS 小鼠模型，Tc（HSA21q;MAC）1Yakaz（“TcMAC21”）。TcMAC21 不是嵌合体，包含 93%可表达和可调节的 HSA21q PCGs。TcMAC21 重现了许多 DS 表型，包括心脏、颅面骨骼和大脑的异常、分子/细胞病理学以及学习、记忆和突触可塑性的损伤。TcMAC21 是现存最完整的 DS 遗传小鼠模型，具有支持广泛基础和临床前研究的潜力。
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