METHOD FOR EXAMINING MUTATION OF Arx GENE RELATED TO X-LINKED LISSENCEPHALY

摘要

PROBLEM TO BE SOLVED: To provide a means for a definite diagnosis of X-linked lissencephaly with abnormal genitalia (XLAG) exhibiting a serious brain structure and a dysfunction.;SOLUTION: Aristaless related homeobox (Arx) gene-deficient mice are prepared so as to elucidate functions of Arx in formation of the forebrain and testis. The male of the mice is lethal and the phenotype thereof closely resembles the XLAG. In short, the miniaturization of the brain and an abnormality in testicular differentiation caused by suppressed cell proliferation and regional deficiencies accompanied thereby in the forebrain are observed in Arx gene-deficient male fetal mice. Furthermore, aberrant migration and differentiation of a GABAergic mediated neuron in the ganglionic eminence and neocortex are observed in the Arx gene-deficient male fetal mice. As a result, partial reproduction of clinical features of the X-linked lissencephaly with the abnormal genitalia (XLAG) is successful in a model animal. Mutations are found in the Arx gene in all 9 specimens by analyzing the Arx gene of patients suffering from the XLAG based on the knowledge.;COPYRIGHT: (C)2004,JPO