2010 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	20500370
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Laboratory animal science
Research Institution	Nagoya University
Principal Investigator	TAKAGISHI Yoshiko Nagoya University, 環境医学研究所, 助教 (50024659)
Co-Investigator(Kenkyū-buntansha)	ODA Senーichi 岡山理科大学, 理学部, 教授 (60023660) HAYASHI Yoshitaka 名古屋大学, 環境医学研究所, 准教授 (80420363)
Project Period (FY)	2008 – 2010
Keywords	疾患モデル / 有髄神経線維 / ミエリン / 軸索
Research Abstract	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.