TARGETED DISRUPTION OF CERULOPLASMIN GENE, AND ITS INFLUENCE ON PANCREATIC B CELL FUNCTION

点击翻译按钮获取中文摘要

The ceruloplasmin (Cp) gene has been shown to be responsible for hereditary Cp deficiency (HCD), which is an autosomal recessive disease characterized by neurological abnormalities. In many HCD cases, type 2 diabetes (DM) was the first symptom of the disease, and 10 - 20 years later at age 40 - 60 the neurological abnormalities occurred. Therefore, we made hypothesis that the Cp gene is a susceptible gene for DM, although the mechanisms involved in the pathogenesis of the development of DM are not clear at present. To clarify this hypothesis an, if it is true, the mechanisms, we first tried to make a mouse, which has targeted disruption of Cp gene (Cp knock out mouse: Cp -/-mouse). Then, this mouse can be used to clarify the mechanisms involved in the pathogenesis of the development of DM.From a mouse genomic library, we screened 2 and 4 clones containing exon 1 and exons 2-4, respectively. These clones were used to make DNA construct. We finally made a DNA construct to knock out exons 2 and 3 of the Cp gene. This DNA construct contains PGK-neo and nLacZ-polyA for selection. We introduced this DNA construct to ES cells to make knock out mouse.