Waddles小鼠遗传性小脑性共济失调突变基因的筛查

目的:探查引起Waddles(Wdl)小鼠遗传性小脑性共济失调的突变基因。方法:采用成年2￣4个月的Wdl小鼠30只和同等数量同胎生的正常小鼠进行运动试验以确认动物模型。应用高通量温度梯度毛细管电泳技术,对Wdl小鼠第4号染色体Wdl基因位点进行PCR及RT-PCR扩增产物的筛查,并用基因测序和RT-PCR的方法来证实突变基因的存在。结果:Wdl小鼠的Car8基因中的第7个外显子扩增产物的分子质量比正常小鼠的扩增产物分子质量小。Wdl小鼠Car8基因的第7个外显子中有19个核苷酸缺失。结论:Wdl小鼠突变基因的发现为探查基因序列异常和运动功能障碍之间的关系开创了新的视角。

The Molecular Mechanism of Hereditary Cerebellar Ataxia in Waddles Mouse

Objective: To discuss the molecular mechanism of hereditary cerebellar ataxia in waddles mouse. Methods: Thirty adult(2-4 months)Wdl mice and 30 wide-type littermates were used for quantitative analyses of motor function. The Wdl locus on mouse Chr 4 was detected by means of high-throughput temperation gradient capillary electrophoresis heterodu-plex examination. The deletion mutation in Car8 exon 7 was confirmed by sequencing and RT-PCR. Results: Car8 exon 7 amplicon was smaller in Wdl mice than that in wild-type littermates. Nineteen nucleotides were deleted within exon 7 of Car8. Conclusion: The research of the mutant gene may provide considerable insight into the fundamental pathophysiological mechanisms of hereditary cerebellar ataxia.