Reiner O, Albrecht U, Gordon M, Chianese K A, Wong C, Gal-Gerber O, Sapir T, Siracusa L D, Buchberg A M, Caskey C T
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
J Neurosci. 1995 May;15(5 Pt 2):3730-8. doi: 10.1523/JNEUROSCI.15-05-03730.1995.
Miller-Dieker lissencephaly syndrome (MDS) is a human developmental brain malformation caused by neuronal migration defects resulting in abnormal layering of the cerebral cortex. LIS1, the gene defective in MDS, encodes a subunit of brain platelet-activating factor (PAF) acetylhydrolase which inactivates PAF, a neuroregulatory molecule. We have isolated murine cDNAs homologous to human LIS1 and mapped these to three different chromosomal loci (Lis1, Lis3, Lis4). The predicted sequences of murine Lis1 protein and its human homolog LIS1 are virtually identical. In the developing mouse and human, Lis1 and LIS1 genes were strongly expressed in the cortical plate. In the adult mouse Lis1 transcripts were abundant in cortex and hippocampus. The direct correlation between cortical defects in MDS patients and Lis1 expression in the murine cortex suggest that the mouse is a model system suitable to study the mechanistic basis of this intriguing genetic disease.
米勒-迪克尔无脑回综合征（MDS）是一种人类发育性脑畸形，由神经元迁移缺陷导致大脑皮质层排列异常引起。LIS1是MDS中的缺陷基因，编码脑血小板活化因子（PAF）乙酰水解酶的一个亚基，该酶可使神经调节分子PAF失活。我们分离出了与人类LIS1同源的小鼠cDNA，并将其定位到三个不同的染色体位点（Lis1、Lis3、Lis4）。小鼠Lis1蛋白及其人类同源物LIS1的预测序列几乎完全相同。在发育中的小鼠和人类中，Lis1和LIS1基因在皮质板中强烈表达。MDS患者的皮质缺陷与小鼠皮质中Lis1表达之间的直接关联表明，小鼠是适合研究这种有趣遗传疾病机制基础的模型系统。
