A morphological study of the brain in the ataxic mutant rat.

一种共济失调突变大鼠，稀释性反张大鼠(DOP)，最初是在Wister大鼠的繁育群体中发现的，表现为毛色变淡和神经障碍，持续抽搐肢体运动和反张紧张性癫痫，直到动物3周大时死亡。这些动物是我们实验室用杂合子(DOP/+)大鼠杂交而成的。利用聚合酶链式反应扩增的微卫星标记将稀释性强直基因定位在8号染色体上，发现APOC3、dop和Mylclv基因连锁，提示该突变与稀释性丘脑的同源。用抗1，4，5-三磷酸肌醇(InsP3)受体抗体的电子显微镜和免疫细胞化学方法发现DOP小脑浦肯野细胞的树突棘中缺少平滑内质网。对发育中的浦肯野细胞的观察表明，SER在胞体和树突中形成，但不在浦肯野细胞的脊椎中形成。SER被认为是细胞内的钙储存，提示突触位置的钙信号过程在突触传递中起关键作用。因此，DOP大鼠被认为是突触调节受损。电子显微镜和免疫细胞化学结果表明，浦肯野细胞轴突终末与小脑深层核团的神经元正常接触。

An ataxic mutant rat, dilute-opisthotonus (dop), was originally discovered in a breeding colony of Wister rats and shows a dilution of coat color and neurological disorders with convulsivelimb movements and opisthotonic seizures continuing until the death of animals at 3 weeks of age. The animals have been bred in our laboratory by intercrossing the heterozygous (dop/+) rats. The dilute-opisthotonus gene was mapped on chromosome 8 by PCR-amplified microsatellite markers, which showed a linkage of Apoc3, dop and Mylclv genes, suggesting that this mutation was homologous to dilute-lethalof the mouse.Electronmicroscopy and immunocytochemistry using anti-inositol 1,4,5-triphosphate (InsP3) receptor antibody revealed that smooth endoplasmic reticulum (SER) was missing in the dendritic spine of Purkinje cell in the dop cerebellum. Observation of developing Purkinje cells showed that SER was formed in the soma and dendrites but not in the spine of the Purkinje cell.SER is assumed to be an intracellular Ca store and it has been suggested that a Ca signaling process at the synaptic site has a key role in synaptic transmission. Thus, the dop rat is thought to have impaired synaptic regulation. Electronmicroscopy and Immunocytochemistry using antibody raised against GABA,transmitter released by Purkinje cell terminals, indicated that Purkinje cell axon terminals normally contacted the neurons in deep cerebellarnuclei.