The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: Positional complementation cloning and extragenic suppression
The vibrator mutation causes neurodegeneration via reduced expression of PITP alpha: Positional complementation cloning and extragenic suppression
复制标题
DOI：
10.1016/s0896-6273(00)80312-8
复制
发表时间：
1997-05-01
期刊：
影响因子：
16.2
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Hamilton, BA;Smith, DJ;Lander, ES
小鼠振动子突变导致早发性进行性震颤，脑干和脊髓神经元变性，以及青少年死亡。我们使用体内位置互补方法克隆了振动子突变，并对振动子及其亲本染色体上产生的76 kb关键区域进行了完全重测序。该突变是在磷脂酰肌醇转移蛋白α基因的内含子4中插入内胆A粒子逆转录子，导致RNA和蛋白质水平降低5倍。振动器中神经丝轻链的表达也减少，提示振动器病理可能存在一种信号通路。振动子表型在一个交叉中被抑制。我们进行了全基因组扫描，并将一个主要抑制基因座（Mvb-1）定位到19号染色体近端。
The mouse vibrator mutation causes an early-onset progressive action tremor, degeneration of brain stem and spinal cord neurons, and juvenile death. We cloned the vibrator mutation using an in vivo positional complementation approach and complete resequencing of the resulting 76 kb critical region from vibrator and its parental chromosome. The mutation is an intracisternal A particle retroposon insertion in intron 4 of the phosphatidylinositol transfer protein alpha gene, causing a 5-fold reduction in RNA and protein levels. Expression of neurofilament light chain is also reduced in vibrator, suggesting one signaling pathway that may underlie vibrator pathology. The vibrator phenotype is suppressed in one intercross. We performed a complete genome scan and mapped a major suppressor locus (Mvb-1) to proximal chromosome 19.