Genetic and physical delineation of the region overlapping the progressive motor neuropathy (pmn) locus on mouse chromosome 13
Genetic and physical delineation of the region overlapping the progressive motor neuropathy (pmn) locus on mouse chromosome 13
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DOI：
10.1006/geno.2001.6595
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发表时间：
2001-07-01
期刊：
影响因子：
4.4
通讯作者：
Guénet, JL
中科院分区：
文献类型：
--
作者：
Martin, N;Jaubert, J;Guénet, JL
小鼠常染色体隐性突变进行性运动神经病(PMN)是一种早期起病的运动神经元病，表现为快速进行性后肢瘫痪、严重的肌肉萎缩和4-6周龄死亡。因此，PMN被认为是运动神经元疾病的一个很好的动物模型，而致病基因的特征应该有助于理解人类脊肌萎缩的生物学原因。在这里，我们报道了基于包含小鼠13号染色体上PMN基因座的高分辨率和高密度遗传图谱的物理图谱的生成。我们已经将PMN基因座和与其协同分离的一组标记定位在0.30 cM的遗传间隔内，由两组标记来描绘。我们已经构建了一个类似于850kb的BAC重叠群，跨越PMN临界区。该BAC重叠群包含小鼠13号染色体与人类1Q和7P区之间的同步性断裂点，为在分子水平上识别这样的断裂点区域奠定了基础。物理和遗传图谱为鉴定位于非重组区间的5个转录单位提供了支持，并为鉴定PMN突变的其他候选基因提供了宝贵的工具。
The mouse autosomal recessive mutation progressive motor neuropathy (pmn) results in early onset motor neuron disease with rapidly progressing hindlimb paralysis, severe muscular wasting, and death at 4-6 weeks of age. pmn is thus considered a good animal model for motor neuron diseases and the characterization of the causative gene should help in understanding the biological causes of human spinal muscular atrophies. Here we report the generation of a physical map based on a high-resolution and high-density genetic map encompassing the pmn locus on mouse chromosome 13. We have positioned the pmn locus and a cluster of markers cosegregating with it within a genetic interval of 0.30 cM, delineated by two clusters of markers. We have constructed an similar to 850-kb contig of BACs spanning the pmn critical region. This BAC contig contains the breakpoint of synteny between mouse chromosome 13 and human 1q and 7p regions and lays the foundation for identifying at the molecular level such a breakpoint region. The physical and genetic maps provided a support for the identification of five transcription units positioned in the nonrecombinant interval, and constitute invaluable tools for the identification of other candidate genes for the pmn mutation.