Ho15J -: A new hotfoot allele in a hot spot in the gene encoding the δ2 glutamate receptor
Ho15J -: A new hotfoot allele in a hot spot in the gene encoding the δ2 glutamate receptor
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DOI：
10.1016/j.brainres.2006.03.068
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发表时间：
2007-04-06
期刊：
影响因子：
2.9
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Motohashi, Junko;Kakegawa, Wataru;Yuzaki, Michisuke
Hotfoot是一种隐性小鼠突变，其特征在于共济失调和后肢的急动运动，是由编码62谷氨酸受体（GluR δ 2）的基因（Grid 2）中的各种突变引起的。到目前为止，至少有20个等位基因，自发产生或通过随机插入转基因，已被描述。有趣的是，大多数hotfoot突变体缺失了一个或多个编码GluR δ 2最氨基末端结构域的外显子。然而，由于大多数热足突变体不再有活的小鼠集落，因此不能排除内含子的一部分丢失可能影响其他外显子的剪接或转录的总体效率的可能性。在这里，我们报告说，一个新发现的hotfoot突变体，hol 5 J，是由Grid 2基因的基因内缺失引起的，这确实导致了一种新型的52个氨基酸的缺失，在最氨基末端结构域的GluR δ 2。与ho 4 J突变体中的GluR δ 2蛋白一样，hol 5 J小鼠中的GluR δ 2蛋白保留在浦肯野细胞的索马中，在那里它们被降解。长期抑郁，一种形式的突触可塑性潜在的信息存储在小脑，被废除，hol 5 J小鼠表现出严重的运动失调的旋转测试。基因组DNA的PCR结果和ho 15 J等位基因的RT-PCR结果之间的一致性支持了grid 2基因组DNA的PCR分析可以预测mRNA和蛋白质的改变的观点。此外，本研究结果强调了最氨基末端结构域在GluR 62信号传导和小脑功能中的重要性。(c)2006 Elsevier B. V.保留所有权利。
Hotfoot, a recessive mouse mutation characterized by ataxia and jerky movements of the hindlimbs, is caused by various mutations in the gene (Grid2) encoding the 62 glutamate receptor (GluR delta 2). So far, at least 20 alleles, arising either spontaneously or through the random insertion of transgenes, have been described. Interestingly, most hotfoot mutants have deletions of one or more exons coding for portions of the most amino-terminal domain of GluR delta 2. However, because live mice colonies are no longer available for most hotfoot mutants, the possibility that the loss of a part of an intron might affect the splicing of other exons or the general efficiency of transcription could not be ruled out. Here, we report that a newly identified hotfoot mutant, hol5J, was caused by an intragenic deletion of the Grid2 gene, which indeed resulted in a new type of 52-amino-acid deletion in the most aminoterminal domain of GluR delta 2. Like GluR delta 2 proteins in ho4J mutants, GluR delta 2 proteins in hol5J mice were retained in the soma of Purkinje cells, where they were degraded. Long-term depression, a form of synaptic plasticity underlying information storage in the cerebellum, was abrogated, and hol5J mice showed severe motor discoordination on rotarod tests. The agreement between the PCR results for genomic DNA and the RT-PCR results for the ho15J allele supports the view that PCR analyses of grid2 genomic DNA can predict alterations in mRNA and protein. In addition, the present findings underscore the importance of the most amino-terminal domain in GluR62 signaling and cerebellar functions. (c) 2006 Elsevier B.V. All rights reserved.