Conditional Ablation and Mutation of Nonmuscle Myosins

非肌肉肌球蛋白重链（NMHC）有三种亚型，即II-A、II-B和II-C。尽管人类非肌肉肌球蛋白II-C的突变（R726 S）导致听力损失，但非肌肉肌球蛋白II-C的功能仍不清楚。使用同源重组，我们产生了非肌肉肌球蛋白II-C突变（R726 S）小鼠，约40%的敲入小鼠在3-5个月大时发生淋巴组织增生性疾病。病鼠的淋巴结、脾脏和胸腺肿大，多个器官内淋巴母细胞增多。肿瘤侵入其他组织。通过FACS分析，来自患病小鼠的淋巴细胞具有大量共表达T细胞标记物和B细胞标记物的细胞，但是使用不同品系的胚胎干细胞产生的第二系小鼠迄今为止没有显示出任何异常。我们正在尝试再生原来的小鼠，看看它们是否会患上这种疾病，我们还将患病小鼠与MRL/MpJ#000486小鼠杂交，这将允许自身免疫异常的完全表达。

There are three isoforms of nonmuscle myosin heavy chain (NMHC), II-A, II-B and II-C. The function of nonmuscle myosin II-C remains unclear though the mutation (R726S) in human nonmuscle myosin II-C result in hearing loss. Using homologous recombination we generated nonmuscle myosin II-C mutant (R726S) mice, and about 40% of the knock-in mice developed a lymphoproliferative disease at 3-5 months old. The sick mice exhibited enlarged lymph nodes, spleens and thymuses and accumulated lymphoblasts in a number of organs. The tumor invaded other tissues. By FACS analysis the lymphocytes from sick mice have a large number of cells that co-express T cell marker and B cell markers, but a second line of mice generated using a different strain of embryonic stem cells fail to show any abnormalities to date. We are trying to regenerate the original mice to see if they will develop the disease, and also we are crossing the sick mice to MRL/MpJ #000486 mice which should allow full expression of the autoimmune abnormalities.