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

对具有 Caspr 突变的跛行小鼠的研究；

• 批准号: 20500370
• 负责人: TAKAGISHI Yoshiko
• 金额: $ 2.66万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20500370/
• 关键词: 疾患モデル; 有髄神経線維; ミエリン; 軸索; 突然変異マウス; 髄神経線維; ランビエ絞輪; パラノード; 免疫組織化学; 電子顕微鏡学

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.

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是髓鞘神经副阳极的主要成分。在突变小鼠的中枢和外周神经系统中发现了神经节/神经节区连接被破坏和离子通道的异常定位，这提示了小鼠神经表型的主要原因。在表现出进行性神经功能缺陷的老年小鼠中，发现轴突含有异常包涵体的改变，并且神经元体的丢失。这些发现提示，副神经节连接处的破坏导致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。

项目成果

A novel Caspr mutation causes the shambling mouse phenotype by disrupting axo-glial interactions of myelinated nerves.

一种新的 Caspr 突变通过破坏有髓神经的轴神经胶质相互作用而导致小鼠出现跛行表型。

• 发表时间: 2009
• 期刊: Journal of Neuropathology and Experimental Neurology 68
• 作者: X.Y.Sun;Y.Hayashi;et al
• 通讯作者: et al

Distribution of neuron-gila interaction at the paranodal junctions in myelinated nerves causes the axonal degeneration and cell death.

有髓神经节旁连接处神经元-吉拉相互作用的分布导致轴突变性和细胞死亡。

• 发表时间: 2010
• 作者: Takagihsi Y;Sun XY;Tobe A;Oda SI;Murata Y.
• 通讯作者: Murata Y.

ホームページ等。

主页等

Disruption of neuron-glia interaction at the paranodal junctions in myelinated nerves causes the axonal degeneration and cell death

有髓神经节旁连接处神经元与胶质细胞相互作用的破坏导致轴突变性和细胞死亡

• 发表时间: 2010
• 作者: Takagishi Y.;Sun X-Y.;Tobe A.;Oda. SL;Murata Y
• 通讯作者: Murata Y

Morphological and functional analysis of the nervous system in shambling mice a Caspr1 mutation.

Caspr1 突变跛行小鼠神经系统的形态学和功能分析。

• 发表时间: 2008
• 作者: Takagishi Y;Okabe E;Chishima Y;Sun XY;Senoo S;Inaba M;Mizumura K;Komatsu Y;Oda SI;Murata Y.
• 通讯作者: Murata Y.