Non-human mammalian animal model for type 2 diabetes

摘要

The present invention provides a non-human mammalian animal model for type 2 diabetes, which spontaneously develops a pathological condition similar to human type 2 diabetes of a non-obese type seen in some Japanese people. The non-human mammalian animal model for type 2 diabetes according to the present invention is deficient in a Cdkal1 gene function on the chromosome of the β cell of the pancreas. More specifically, the non-human mammalian animal model for type 2 diabetes may be produced by interbreeding a non-human mammal carrying a site-specific recombination enzyme recognition sequence in the 3′-untranslated region and the 5′-untranslated region of a particular domain carrying one exon or more exons of the Cdkal1 gene with a non-human mammal in which a gene of a site-specific recombination enzyme capable of recognizing the site-specific recombination enzyme recognition sequence and splicing out the particular domain is inserted in such a manner as expressing specifically at a site downstream of a promoter of a gene expressing specifically in the pancreas.

主权项

1. A transgenic mouse whose genome comprises a homozygous inactivation of the CDK5 regulatory subunit associated protein 1-like 1 (Cdkal1) gene in cells of the pancreas such that no Cdkal1 protein is produced in said cells,
wherein said transgenic mouse after being fed a high fat diet containing fat at an amount of 45% of the total calories for three weeks exhibits a phenotype, wherein said phenotype comprises a higher blood glucose level and a lower level of insulin secretion when compared to a wild type mouse fed said high fat diet, or when compared with said wild type mouse fed a low fat diet, or said transgenic mouse fed a low fat diet, wherein said low fat diet contains fat at an amount of 10% of the total calories.