Development of gene therapy by the retrograde axonal transport of adenovirus into the reeler mouse

点击翻译按钮获取中文摘要

In this project, we aimed to develop the efficient introduction of exogeneous genes into the central nervous system of the neurological mutant mice, reeler and yatari. The reeler and yotari mouse are auto somal recessive, mutant mice, caused by mutation of reelin and disabled, homolog l (Dab1) gene, respectively. The mutant mouse is recognized by unstable gait and tremor and by \ I early deaths, around at the time of weaning. The cytoarchitectures of cerebeller and cerebral cortices and hippocampal formation of the reeler and yotari mouse are abnormal. In the present study, Lac-Z recombinant adenovirus was injected into the motor crtex of the normal, reeler, and yotari mice to examine how the virus is efficiently incorporated into the nervous system of the experimental animals. In the contralateral cortex, callosal commissure neurons were retrogradely labeled by the lac-Z recombinant adenovirus. The distribution pattern of CG neurons of the yotari was similar to that of the reeler : retrogradely labeled CG neurons were seen throughout all depths of the contralateral Fr1. We clarified that the small volume of the viral solution (〜0.02ul) is enough for the retrograde infection of neurons in the coerebral cortex both in the normal and reeler-phenotype mutants.