Molecular mechanisms of thrombosis in mouse model induced by age and stress

May-Hegglin异常是编码A型细胞肌球蛋白重链（NMMHCA）的MYH 9基因异常综合征，是一种以血小板巨大、血小板减少和白色血细胞包涵体为特征的巨血小板减少症的典型疾病。特发性血小板减少性紫癜（ITP）的诊断存在与巨血小板减少症相同的问题，为了避免不必要的治疗，需要建立适当的鉴别诊断。本研究对先天性巨血小板减少症患者外周血标本中的NMMHCA包涵体类型进行了研究，使用抗NMMHCA抗体进行免疫染色分析，怀疑MYH 9异常，分析，并从免疫染色结果的类型中鉴定该区域中的基因异常。因此，表明NMMHCA的免疫染色分析可用作MYH 9异常综合征的简便筛查方法。此外，用基因诱捕法破坏MYH 9基因的纯合NMMHCA基因敲除小鼠具有胚胎致死性，提示NMMHCA是小鼠胚胎早期发育不可缺少的分子。虽然听性脑干反应（ABR）降低似乎是与杂合子小鼠中MYH 9异常的Alport症状相对应的症状，但在HE染色和电子显微镜图像中没有异常。因此，小鼠敲入分析对于研究MYH 9异常的表型是必要的。另一方面，提示杂合子R702 C敲入小鼠在嵌合体小鼠交配中的出生率极低（可能是因为母亲进食？），与野生型相比，它的体质较弱。

May-Hegglin anomaly, a typical disease of the macrothrombocytopenia characterized in the giant platelet, the decrease of platelets, and the white blood corpuscle inclusion body, is an abnormality syndrome of the MYH9 gene coding the A type cell myosin heavy chain (NMMHCA). The problem diagnosed as the idiopathic thrombocytopenic purpura (ITP) is pointed out as for the macrothrombocytopenia, and the establishment of adequate discrimination diagnostics is required to evade needless treatment.In this research, the type of the NMMHCA inclusion body on the peripheral-blood specimen of the congenital macrothrombocytopenia patient, from which the MYH9 abnormality was doubted by the immunostaining analysis using the anti-NMMHCA antibody, was analyzed, and the gene abnormality was identified in the area from the type of the immunostaining result. Thus, it was shown that the immunostaining analysis of NMMHCA was useful as a handy screening method of the MYH9 abnormality syndrome. In addition, it was suggested that NMMHCA was an indispensable molecule to growth at the early stage of mouse embryo, because the homozygous NMMHCA knock out mouse, which the MYH9 gene was destroyed by the gene-trap method, was embryonic lethal. Although the auditory brain stem response (ABR) decrease seemed to be an symptom corresponding to the Alport symptom of the MYH9 abnormality in a heterozygous mouse, there was no abnormality in the HE staining and electron microscope image. It seemed that the knock in mouse analysis was necessary to investigate the phenotype of MYH9 abnormality. On the other hand, it was suggested that the heterozygous R702C knock in mouse was extremely low birth rate in the chimera mouse mating (probably because of eating by mother?), and it had a weak constitution compared with a wild type.