Hamilton B A, Smith D J, Mueller K L, Kerrebrock A W, Bronson R T, van Berkel V, Daly M J, Kruglyak L, Reeve M P, Nemhauser J L, Hawkins T L, Rubin E M, Lander E S
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Neuron. 1997 May;18(5):711-22. doi: 10.1016/s0896-6273(00)80312-8.
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.
小鼠震颤器突变会导致早发性进行性动作震颤、脑干和脊髓神经元退化以及幼年死亡。我们使用体内定位互补方法克隆了震颤器突变，并对来自震颤器及其亲代染色体的76 kb关键区域进行了完全重测序。该突变是磷脂酰肌醇转移蛋白α基因内含子4中的一个脑池内A颗粒反转录转座子插入，导致RNA和蛋白质水平降低5倍。震颤器中神经丝轻链的表达也降低，提示了一条可能是震颤器病理基础的信号通路。在一次杂交中，震颤器表型受到抑制。我们进行了全基因组扫描，并将一个主要抑制基因座（Mvb-1）定位到近端19号染色体。
