• J Yunus, T Setsu, S Kikkawa, T Sakisaka, and T Terashima.
• Division of Developmental Neurobiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-1, Chuo-ku, Kobe 650-0017, Japan.
• Neuroscience. 2014 Sep 5;275:259-71.

AbstractThe laggard (lag) mutant mouse, characterized by hypomyelination and cerebellar ataxia, is a spontaneously occurring mutant mouse caused by mutation in the Kif14 gene. In this mutant mouse, the laminated structures such as the cerebral and cerebellar cortices and the dentate gyrus are cytoarchitecturally abnormal. Macroscopically, the olfactory bulb of the lag mutant mouse is smaller in size and more transparent than the normal counterpart. Hematoxylin-eosin staining reveals that the mutant olfactory bulb has normal lamination in general, but detailed analysis has demonstrated that olfactory periglomerular cells and granule cells are reduced in number. In the mutant, olfactory glomeruli are cytoarchitecturally disorganized and mitral cells are arranged in multiple cell layers instead of being arranged in a single layer. The rostral migratory stream in the mutant becomes gradually thinner or obliterated during early postnatal days. Some of mitral cells and periglomerular cells are multinucleated, suggesting that Kif14 mutation leads to an abnormal cell division. In the mutant, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the subventricular zone of the lateral ventricle are increased in number, especially at perinatal age, suggesting that the decreased population of granule cells in the lag mutant mouse is caused by the increased apoptotic cell death. The olfactory input appears to be intact, as indicated by anterograde labeling of olfactory nerves with an injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the olfactory mucosa. In conclusion, the olfactory bulb of the lag mutant mouse is cytoarchitecturally affected, suggesting that the causal gene for lag mutation, i.e., Kif14, has multiple effects on the development of laminated structures in the central nervous system in addition to the myelin formation.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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