Kokubun T
Department of Otopharyngolaryngology, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1991 May;66(3):333-47.
The 'Wriggle Mouse Sagami (WMS)' is a new neurological mutation that was discovered in an inbred strain of BALB/c mice at the Ohmura Institute for Laboratory Animals (Address: Zama 228, Kanagawa, Japan) in 1984. The affected characteristics are transmitted by an autosomal recessive gene (wri). The clinical symptoms are characterized by dystonic involuntary movements, such as fine tremors of the forelimbs, hypertonic musculature of the extremities, difficulty in maintaining an upright posture, writhing of the trunk, wriggling of the neck up-and-down and from side to side without any coordination between the movements of the limbs and trunk, and inability to walk a staigho that begin at 10 days to 2 weeks after birth and are progressive until 12 weeks of age. Here a morphological study on the brain of the WMS with special reference to the cerebellum was intended. The results were as follows: (1) In spite of these severe clinical symptoms, no marked abnormalities were observed in the cyto- and myeloarchitecture of the central nervous system, although the size of the whole brain was somewhat reduced and the molecular layer of the cerebellum was relatively hypotrophic compared with the granule cell layer. (2) The motor tracts investigated were normally detected by the retrograde HRP-labeling method. (3) Slight abnormality of the dendritic trees and spines, and remarkable axonal swellings of the Purkinje cells were demonstrated by a sensitive immunohistochemical method for inositol 1,4,5-trisphophate receptor protein (P400 protein). These changes were also evaluated by the Golgi method. (4) In electron microscopy of the molecular layer of the WMS cerebellum, parallel fibers seemed to be reduced and shrunken, and their synaptic contacts on the dendritic spines of the Purkinje cells were clearly reduced even at 17 days after birth. (5) Consequently, the Purkinje cells were possibly affected by failure of accurate connection with input fibers or by synaptic dysfunction, which might occur over the entire central nervous system.
“和歌山扭动小鼠（WMS）”是1984年在大村实验动物研究所（地址：日本神奈川县座间市228号）的近交系BALB/c小鼠中发现的一种新的神经学突变体。受影响的特征由常染色体隐性基因（wri）传递。临床症状的特点是张力障碍性不自主运动，如前肢细微震颤、四肢肌肉张力亢进、难以保持直立姿势、躯干扭动、颈部上下及左右扭动且四肢与躯干运动之间缺乏任何协调性，以及无法直线行走，这些症状在出生后10天至2周开始出现，并持续进展直至12周龄。在此，旨在对WMS小鼠的大脑进行形态学研究，特别关注小脑。结果如下：（1）尽管有这些严重的临床症状，但中枢神经系统的细胞结构和髓鞘结构未观察到明显异常，不过全脑体积有所减小，与颗粒细胞层相比，小脑分子层相对发育不良。（2）通过逆行HRP标记法正常检测到所研究的运动束。（3）用针对肌醇1,4,5 - 三磷酸受体蛋白（P400蛋白）的灵敏免疫组织化学方法显示，浦肯野细胞的树突分支和棘有轻微异常，且轴突明显肿胀。这些变化也通过高尔基法进行了评估。（4）在WMS小鼠小脑分子层的电子显微镜观察中，平行纤维似乎减少并萎缩，即使在出生后17天，它们与浦肯野细胞树突棘上的突触接触也明显减少。（5）因此，浦肯野细胞可能受到与输入纤维精确连接失败或突触功能障碍的影响，这种情况可能在整个中枢神经系统中发生。
