A null mutation in inositol polyphosphate 4-phosphatase type I causes selective neuronal loss in weeble mutant mice
A null mutation in inositol polyphosphate 4-phosphatase type I causes selective neuronal loss in weeble mutant mice
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DOI：
10.1016/s0896-6273(01)00468-8
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发表时间：
2001-10-25
期刊：
影响因子：
16.2
通讯作者：
Frankel, WN
中科院分区：
文献类型：
--
作者：
Nystuen, A;Legare, ME;Frankel, WN
Weeble突变小鼠具有严重的运动不稳定和显著的小脑和海马CA1区神经元丢失。利用遗传图谱将突变定位于编码肌醇多磷酸4-磷酸酶I型(Inpp4a)的基因，其中单核苷酸缺失导致可能的零等位基因。INPP4A的底物是影响细胞内钙释放的中间产物，但也通过结合Akt原癌基因参与细胞周期调节；两者中的任何一个的功能障碍都可能解释WEWBLE小鼠的神经元丢失。尽管磷脂酶的其他突变与突触缺陷有关，而不会导致神经元丢失，但Weble表明，Inpp4a对于小鼠出生后发育期间的一部分神经元的生存至关重要。
Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are intermediates in a pathway affecting intracellular Ca2+ release but are also involved in cell cycle regulation through binding the Akt protooncogene; dysfunction in either may account for the neuronal loss of weeble mice. Although other mutations in phosphoinositide enzymes are associated with synaptic defects without neuronal loss, weeble shows that Inpp4a is critical for the survival of a subset of neurons during postnatal development in mice.