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

May-Hegglin异常是一种编码a型细胞肌球蛋白重链（NMMHCA）的MYH9基因异常综合征，是一种典型的以巨大血小板、血小板减少、白细胞包涵体为特征的巨血小板减少症。针对大量血小板减少症，指出诊断为特发性血小板减少性紫癜（ITP）的问题，需要建立充分的鉴别诊断，以避免不必要的治疗。本研究利用抗NMMHCA抗体免疫染色分析怀疑MYH9异常的先天性巨血小板减少症患者外周血标本中NMMHCA包涵体的类型进行分析，并根据免疫染色结果的类型确定该区域的基因异常。因此，NMMHCA的免疫染色分析是一种简便的MYH9异常综合征筛查方法。此外，NMMHCA是小鼠胚胎早期生长不可缺少的分子，因为纯合的NMMHCA敲除小鼠，MYH9基因被基因陷阱法破坏，具有胚胎致死性。听觉脑干反应（ABR）下降似乎是杂合小鼠MYH9异常的Alport症状对应的症状，但HE染色和电镜图像均未见异常。似乎敲入小鼠分析是必要的，以研究MYH9异常的表型。另一方面，提示杂合子R702C敲入小鼠在嵌合体小鼠交配中的出生率极低（可能是被母体吃掉的原因），且与野生型相比体质较弱。

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.