Neurobiological effects of a null mutation depend on genetic context:: Comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor
Neurobiological effects of a null mutation depend on genetic context:: Comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor
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DOI：
10.1016/s0306-4522(01)00193-2
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Mariani, J
中科院分区：
文献类型：
--
作者：
Lalouette, A;Lohof, A;Mariani, J
Hotfoot是一种具有共济失调表型的突变小鼠，已被证明是由于网格中的突变所致。基因本文通过比较两个Grid 2等位基因：Grid 2（ho-4J）和Grid 2（ho-Nancy）的分子、形态、电生理和行为学特征，首次发现这两个突变均为基因开放阅读框的缺失，并且在突变小脑提取物中未检测到GRID 2蛋白，提示这两个等位基因为null样突变。形态学和电生理学分析表明，两种菌株之间没有明显的差异：两种菌株都表现出裸露的浦肯野树突棘和突触前活动区和突触后分化特征的hotfoot突变的长度之间的不匹配;和相同的低水平（20%）的浦肯野细胞的多攀爬纤维神经支配被发现在两种菌株。只有运动行为的差异，发现两种菌株之间。Grid 2（ho-4J）小鼠显示出比Grid 2（ho-Nancy）小鼠更严重的共济失调，并且尽管两种品系都显示出通过训练改善其运动任务表现的明显能力，但Grid（ho-4J）表现仍然非常差，而Grid 2（ho-Nancy）小鼠接近对照水平。这两个品系之间唯一的区别是它们的遗传背景，我们的研究结果表明，在分析突变小鼠的感觉运动性能时，必须考虑遗传背景。(C)2001年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Hotfoot is a mutant mouse with an ataxic phenotype which has been shown to be due to a mutation in the Grid.? gene. In this paper, we compare molecular, morphological, electrophysiological and behavioral features of two Grid2 alleles: Grid2(ho-4J) and Grid2(ho-Nancy) first show that these two mutations are deletions in the open reading frame of the gene and that no GRID2 protein is detectable in extracts of mutant cerebella, suggesting that the two alleles are null-like mutations. Morphological and electrophysiological analyses reveal no obvious differences between the two strains: both strains showed the naked Purkinje dendritic spines and mismatch between the length of the presynaptic active zone and postsynaptic differentiation characteristic of the hotfoot mutation; and the same low level (20%) of multiple climbing fiber innervation of Purkinje cells was found in both strains. Only differences in motor behavior were found between the two strains. The Grid2(ho-4J) mouse shows more severe ataxia that the Grid2(ho-Nancy) mouse and, although both strains show a clear capacity to improve their performance of a motor task with training, the Grid(ho-4J) performance remains very poor whereas Grid2(ho-Nancy) mice approach control levels. The only difference between the two strains is their genetic background.Our results show that the genetic background must be taken into account when analyzing sensorimotor performances of mutant mice. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.