Physiological role and effect of (CTG) n of myotonin protein kinase, the product of myotonic dystrophy gene.

强直性肌营养不良基因产物肌强直蛋白激酶(CTG)n的生理作用和作用。

基本信息

批准号：
06670682
负责人：
TSUKAHARA Toshifumi
金额：
$ 1.28万
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 General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670682/
关键词：
Myotonic dystrophy Myotonin protein kinase Fusion protein Specific antiserum Western blot CTG repeats

项目摘要

Myotonin protein kinase is the product of the gene that causes Myotonic dystrophy. There were contradictory results on quantities of myotonin protein kinase in MD patients. To clarify whether the protein decrease or increase in the patients, we generated a fusion protein of myotonin protein kinase, and antisera against the fusion protein or peptides deduced from myotonin protein kinase cDNA.By western blot analysis using the antibody identified a specific 53kDa-myotonin protein kinase band, we found decreases in the amount of the protein in skeletal muscle of MD patients about in half. The amount of myotonin protein kinase showed negative correlation with the length of (CTG) n in MD patients. The result demonstrates that the decrease of the enzyme relates to the seriousness of the disease. Further, the antibody recognized a 62kDa protein in cardiac muscle and 53kDa and 62kDa proteins in brain, suggesting that there are tissue specific isoforms in myotonin kinase.To investigate the mechanism of CTG repeats expansion, myoblasts from MD patients were cultured long term. However, there was no change in the length of (CTG) n during the passages. Therefore, the somatic heterogeneity of CTG repeats in MD patients seems to occur before symptom.Since the fusion protein we generated is coverd the most part of myotonin protein kinase, we got some requests from abroad. We served our fusion protein by the requests and could contribute to the research.

肌醇蛋白激酶是引起肌发育症的基因的产物。在MD患者中，肌醇蛋白激酶的量矛盾。 To clarify whether the protein decrease or increase in the patients, we generated a fusion protein of myotonin protein kinase, and antisera against the fusion protein or peptides deduced from myotonin protein kinase cDNA.By western blot analysis using the antibody identified a specific 53kDa-myotonin protein kinase band, we found decreases in the amount of the protein in skeletal muscle of MD patients about in 一半。 MD患者的肌醇蛋白激酶的量与（CTG）N长度的长度相关。结果表明，酶的减少与疾病的严重性有关。此外，抗体在心脏肌肉中识别了62KDA蛋白，大脑中的53KDA和62KDA蛋白表明，肌醇激酶中存在组织特异性同工型。研究CTG重复重复扩展的机制，长期培养了MD患者的成肌细胞。但是，通过（CTG）N期间的长度没有变化。因此，MD患者中CTG重复的体细胞异质性似乎发生在症状之前。由于我们产生的融合蛋白是肌醇蛋白激酶的大部分，因此我们从国外收到了一些请求。我们根据要求为融合蛋白服务，并可能有助于研究。