Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement:: hematological, nephrological, and otological studies of heterozygous KO mice
Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement:: hematological, nephrological, and otological studies of heterozygous KO mice
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DOI：
10.1016/j.bbrc.2004.10.147
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发表时间：
2004-12-24
影响因子：
3.1
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Matsushita, T;Hayashi, H;Saito, H
在非肌肉肌球蛋白重链（NMMHC）的三种不同亚型中，只有NMMHCA与称为MYH 9疾病的遗传性人类疾病相关，其特征在于巨血小板减少症和特征性粒细胞包涵体。在这里，进行靶向基因破坏以了解NMMHCA，MYH 9基因的基本和病理作用。杂合杂交产生的552个新生儿中没有纯合动物，这表明MYH 9的表达是胚胎发育所必需的。相比之下，MYH 9 +/-小鼠存活且可生育，没有大体解剖学、血液学和肾脏学异常。免疫荧光分析也显示NMMHCA的正常胞浆分布。我们进一步测量了听觉脑干反应，发现六只MYH 9 +/-小鼠中有两只有听力损失，而其余四只与野生型小鼠相当。这种观察可能与MYH 9疾病人类个体的Alport表现的多样性表达平行，并表明该基因对特定器官的维持和功能的有限需求。(C)2004年爱思唯尔公司All rights reserved.
Among three different isoforms of non-muscle myosin heavy chains (NMMHCs), only NMMHCA is associated with inherited human disease, called MYH9 disorders, characterized by macrothrombocytopenia and characteristic granulocyte inclusions. Here targeted gene disruption was performed to understand fundamental as well as pathological role of the gene for NMMHCA, MYH9. Heterozygous intercrosses yielded no homozygous animals among 552 births, suggesting that MYH9 expression is required for embryonic development. In contrast, MYH9+/- mice were viable and fertile without gross anatomical, hematological, and nephrological abnormalities. Immunofluorescence analysis also showed the normal cytoplasmic distribution of NMMHCA. We further measured the auditory brainstem response and found two of six MYH9+/- mice had hearing losses, whereas the remaining four were comparable to wild-type mice. Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs. (C) 2004 Elsevier Inc. All rights reserved.