Genetic analyses of motor ataxia mutant mice

运动共济失调突变小鼠的遗传分析

• 批准号: 18500337
• 负责人: MASUYA Hiroshi
• 金额: $ 2.57万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500337/
• 关键词: Motor coodination; MutaReneis; Positional clonin; Hermansky-Pudlak Syndrome; Coat color; dilution of skin color; Disease model animal; Mouse; モデル動物; 運動失調; 突然変異; 染色体マッピング; 電気生理解析; 連鎖解析; Motor coodination; MutaReneis; Positional clonin; Hermansky-Pudlak Syndrome; Coat color; dilution of skin color; Disease model animal; Mouse; モデル動物; 運動失調; 突然変異; 染色体マッピング; 電気生理解析; 連鎖解析

We worked out genetic mapping of five ataxia mutants derived from a large-scale mutagenesis program. As a result, M100612, M100651, M100718, M101243, M101479 were mapped on chromosomes 10, 2, 2, 11 and 6 respectively. Rotor rod analysis revealed that heterozugotes of four of five mutants showed obvious defect on motor coordination except for M101479. We worked out detailed analyses on M100651 which shows obvious ataxia and dilution of coat color. The cerebellum shows no morphological change of neuronal cells and their alignments. The cerebellum also showed any abnormalities in electrophysiologic analysis of the cerebellum. We worked out fine mapping analysis of M100651 with 591 progeny from the backcross ( (C57FIL/6J x DBA/2J)F1-M100651/+ x DBA/2J). As a result, M100651 was mapped on 7.2Mb (7152197bp) interval between genetic markers D21Mit484 (118399166-118399277bp) and D2Mit398 (125551330-125551474). We have searched candidate gene for M100651 mutation with a web-based knowledge base search system, PosMed (http://omicspace.riken.jp/PosMed/). A candidate gene for Hermansky-Pudlak Syndrome, Pldn is one of the candidate of M100651.

我们制定了来自大规模诱变程序的五个共济失调突变体的遗传图。结果，分别在染色体10、2、2、11和6上映射了M100612，M100651，M100718，M101243，M101479。转子杆分析表明，除M101479外，五个突变体中四个突变体中有四个突变体中有四个杂糖蛋白显示出明显的缺陷。我们对M100651进行了详细的分析，该分析显示出明显的共济失调和外套颜色稀释。小脑没有神经元细胞及其比对的形态变化。小脑在小脑的电生理分析中还显示出任何异常。我们从反向交叉（（（C57fil/6J X dBA/2J）F1-M100651/+ X DBA/2J）的M100651进行了精细的映射分析。结果，将M100651映射在遗传标志物D21MIT484（118399166-118399277BP）和D2MIT398（1255551330-1255551474）之间的遗传标志物D21MIT484（118399166-118399277BP）之间映射。我们已经使用基于Web的知识基础搜索系统（http://omicspace.riken.jp/posmed/）搜索了M100651突变的候选基因。 PLDN是Hermansky-Pudlak综合征的候选基因，是M100651的候选人之一。