ヒト非肥満インスリン非依存型糠尿病の動物モデルN0Nマウスのプレプ口インスリン遺伝子のクローニングとその構造解析

摘要

We have proposed in the previous study that the NON mouse is an animal model suitable for studying human non-obese, non-insulin-dependent diabetes mellitus, and we have shown that hypoinsulinemia in the NON mouse was associated with reduced levels of insulin mRNA in their pancreas.These results suggest that structural alternation of the insulin gene may occur in this mouse.In the present study, to corroborate this possibility, we attempted to isolate and characterize the insulin gene of the NON mouse.Comparison with structures of the insulin I and II genes of the BALB/c mouse demonstrated that the NON mouse has two non-allelic insulin genes, encoding separately insulin I and II.The nucleotide sequences of the NON mouse insulin genes, including 5u27-transcriptional regulatory region and exon/intron organization, do not differ from the reported sequences of the insulin I and II genes of the BALB/c mouse.We can, however, point out that about 100 base pairs additional sequence and 7 point mutations are involved in further upstream 5u27-flanking region of, and 3 point mutations in 3u27-flanking region of the insulin II gene of the NON mouse.We conclude that the reduced expression of the insulin genes in the NON mouse is due to neither the structural change in the known transcriptional regulatory elements nor occurrence of the abnormal and unstable insulin mRNA.Role of the 5u27-upstream additional sequence for the insulin II gene expression remains to be elucidated.