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PRODUCTION OF MYOPHATIC MODEL MICE WITH GENETIC CAVEOLIN-3 DEFICIENCY AND PHATHOLOGICAL ANALYSIS OF THEIR MUSCLES

CAVEOLIN-3基因缺陷型肌病模型小鼠的制作及其肌肉病理学分析

基本信息

批准号：
10670224
负责人：
HAGIWARA Yasuko
金额：
$ 2.11万
依托单位：
NATIONAL INSTITUTE OF NEUROSCIENCE NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670224/
关键词：
CAVEOLIN-3 GENE KNOCK-OUT MICE MUSCULAR DYSTROPHY SKELETAL MUSCLE カベオリン-1 心筋平滑筋

项目摘要

Caveolin-3 is a muscle-specific protein integrated in the caveolae, which are small invaginations of the plasma membrane. Mutations of the caveolin-3 gene, localized at 3p25, have been reported to be involved in the pathogenesis of limb-girdle muscular dystrophy(LGMDIC or caveolinopathy) with mild clinical symptoms, inherited through autosomal dominant form of genetic transmission. To elucidate the pathogetic mechanism, we developed caveolin-3-deficient mice for use as animal models of caveolinopathy. Caveolin-3 mRNA and its protein were absent in homozygous mutant mice. In heterozygous mutant mice, both the mRNA and its protein were normal in size, but their amounts reduced by about half. The density of caveolae in skeletal muscle plasma membrane was roughly proportional to the amount of caveolin-3. In homozygous mutant mice, muscle degeneration was recognized in soleus muscles at 8 weeks of age and in the diaphragm from 8 weeks to 30 weeks, although there was no difference in growth and movement between wild-type and mutant mice. No apparent muscle degeneration was observed in heterozygous mutant mice, indicating that pathological changes caused by caveolin-3 gene disruption were inherited through the recessive form of genetic transmission.

小窝蛋白-3是一种整合在小泡中的肌肉特异性蛋白，小泡是质膜的小内陷。据报道，定位于3p25的小窝蛋白-3基因突变与肢体带状肌营养不良（LGMDIC或小窝蛋白病）的发病机制有关，具有轻微的临床症状，通过常染色体显性遗传形式遗传。为了阐明其致病机制，我们建立了小洞蛋白-3缺陷小鼠作为小洞蛋白病的动物模型。在纯合子突变小鼠中不存在caveolin - 3mrna及其蛋白。在杂合突变小鼠中，mRNA及其蛋白的大小都是正常的，但它们的数量减少了大约一半。骨骼肌质膜小窝的密度与小窝蛋白-3的含量大致成正比。在纯合子突变小鼠中，8周龄的比目鱼肌和8周龄至30周龄的膈肌可以识别出肌肉变性，尽管野生型和突变型小鼠在生长和运动方面没有差异。杂合突变小鼠未见明显的肌肉退行性变，说明小窝蛋白-3基因破坏引起的病理改变是通过隐性遗传方式遗传的。