Fransen E, D'Hooge R, Van Camp G, Verhoye M, Sijbers J, Reyniers E, Soriano P, Kamiguchi H, Willemsen R, Koekkoek S K, De Zeeuw C I, De Deyn P P, Van der Linden A, Lemmon V, Kooy R F, Willems P J
Department of Medical Genetics, University of Antwerp, B-2610 Antwerp, Belgium.
Hum Mol Genet. 1998 Jun;7(6):999-1009. doi: 10.1093/hmg/7.6.999.
L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.
L1是一种神经细胞粘附分子，主要参与大脑发育过程中的轴突导向和神经元迁移。人类L1基因突变会导致复杂的临床症状，包括智力迟钝、神经学异常以及不同程度的脑积水。最近，构建了一种L1基因靶向无效突变的转基因小鼠模型。这些基因敲除（KO）小鼠表现出皮质脊髓束发育不全。在此，我们对这些KO小鼠进行了进一步研究，包括脑部磁共振成像、神经病理学分析和行为测试。结果显示脑室系统异常，侧脑室和第四脑室扩张，中脑导水管形状改变。此外，KO小鼠的小脑蚓部发育不全。它们的探索行为表现为刻板的外周转圈，类似于诱导性小脑损伤的啮齿动物。
