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

在这个项目中，我们的目标是发展将外源基因高效地导入神经系统突变小鼠、卷尾鼠和雅塔利鼠的中枢神经系统。Reeler和yotari小鼠分别是由reelin基因突变引起的自体隐性遗传突变小鼠和同源的残疾L(Dab1)基因突变小鼠。突变的小鼠通过不稳定的步态和颤抖以及断奶时的早期死亡来识别。小脑、大脑皮层和海马区的细胞构筑异常。在本研究中，将Lac-Z重组腺病毒注射到正常、卷曲和yotari小鼠的运动皮质中，以检测该病毒如何有效地整合到实验动物的神经系统中。在对侧大脑皮质，用Lac-Z重组腺病毒逆行标记了扣带连合区神经元。Yotari的CG神经元的分布模式与卷轴相似：逆行标记的CG神经元遍及对侧Fr1的所有深度。我们澄清了病毒溶液的小体积(~0.02ul)足以使正常和卷曲表型突变的大脑皮质神经元逆行感染。

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.