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.

带有CASPR基因突变的Shambling（SHM）小鼠在出生后2-3周时表现出共济失调和后肢parasis。 CASPR是髓神经中偏码的主要组成部分。在突变小鼠的中央和周围神经系统中发现了离子通道的偏an道路连接和异常定位，这表明小鼠神经系统表型的主要原因。在显示出进行性神经系统缺陷的老年小鼠中，发现含有异常夹杂物的轴突改变，此外，还发现了神经元的损失。这些发现表明，偏dy处的偏an道路连接会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

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.

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 with a Casprl mutation

Casprl 突变跛行小鼠神经系统的形态和功能分析

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

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.