Molecular definition of an allelic series of mutations disrupting the mouse Lmx1a (dreher) gene
Molecular definition of an allelic series of mutations disrupting the mouse Lmx1a (dreher) gene
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DOI：
10.1007/s00335-006-0033-7
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发表时间：
2006-10-01
期刊：
影响因子：
2.5
通讯作者：
Millen, Kathleen J.
中科院分区：
文献类型：
--
作者：
Chizhikov, Victor;Steshina, Ekaterina;Millen, Kathleen J.
dreher （dr）突变纯合子小鼠的特征是色素沉着和骨骼异常，以及引人注目的行为表型，包括共济失调、前庭功能缺陷和多动。共济失调与小脑畸形有关，小脑畸形与人类的丹迪-沃克畸形非常相似。此前，定位克隆在3个dr等位基因中发现了LIM同源盒转录因子1 α基因（Lmx1a）突变。然而，其中两个等位基因已经灭绝，无法进行进一步分析。在本文中，我们报道了一个新的自发性dr等位基因，并描述了该基因和另外六个dr等位基因中的Lmx1a突变。引人注目的是，这些等位基因的缺失、错义和移码突变都会导致类似的小脑畸形，这表明迄今为止分析的所有dr突变都是空等位基因。
Mice homozygous for the dreher (dr) mutation are characterized by pigmentation and skeletal abnormalities and striking behavioral phenotypes, including ataxia, vestibular deficits, and hyperactivity. The ataxia is associated with a cerebellar malformation that is remarkably similar to human Dandy-Walker malformation. Previously, positional cloning identified mutations in LIM homeobox transcription factor 1 alpha gene (Lmx1a) in three dr alleles. Two of these alleles, however, are extinct and unavailable for further analysis. In this article we report a new spontaneous dr allele and describe the Lmx1a mutations in this and six additional dr alleles. Strikingly, deletion null, missense, and frameshift mutations in these alleles all cause similar cerebellar malformations, suggesting that all dr mutations analyzed to date are null alleles.