A study of shambling mice with a Caspr mutation ; as a model for the neurodegenerative disease

具有Caspr基因突变的shambling（shm）小鼠在出生后2~3周龄出现共济失调和后肢轻瘫。Caspr是有髓神经中副阳极的主要成分。在突变小鼠的中枢和外周神经系统中发现了破坏的结旁连接和在结/结旁区域的离子通道的异常定位，这表明小鼠神经系统表型的主要原因。在进行性神经功能缺损的老龄小鼠中，发现了含有异常包涵体的轴突改变，进而出现神经元胞体的缺失，这些发现表明旁阳极的旁结连接破坏导致了轴突变性和神经元细胞死亡，因此shm小鼠是人类神经退行性疾病的潜在动物模型。

The shambling (shm) mouse with mutation of a Caspr gene exhibits ataxia and hind limb paresis at 2～3 weeks of age after birth. Caspr is a major component of the paranode in myelinated nerves. Disrupted paranodal junctions and aberrant localization of ion channels at the nodal/paranodal regions were found in the central and peripheral nervous system of mutant mice, suggesting a major cause of the mouse neurological phenotype. In aged mice showing progressive neurological deficits, altered axons containing abnormal inclusions and, further, a loss of neuronal somata were found. These findings suggest that the disrupted paranodal junction at the paranode causes the axonal degeneration and neuronal cell death, thus the shm mice is a potential animal model for human neurodegenerative disease.