动物造模,药效评价,糖尿病 z-bio 2024-08-07 308

　　Bruning et al. introduced ineffective alleles of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) to mice through double heterozygosity, resulting in a decrease in IR/IRS-1 expression in the mice. After 4-6 months, 40% of the mice developed dominant diabetes, accompanied by hyperinsulinemia and islet B cell proliferation, and had obvious insulin resistance. It was confirmed that IR and various defects in its signal transduction chain had synergistic effects.

　　Bali et al. replaced exon II of the mouse glucokinase (GCK) gene with a neomycin resistance gene to create a target vector and heterozygous it into normal mice, resulting in GK+/- mice. It was found that the glucose tolerance of the mouse was decreased, and the glucose sensitivity of hepatocytes and islet B cells was low. The disease caused by the decreased GCK activity of islet B cells and hepatocytes was similar to that of human adolescent onset adult diabetes (MODY), which could be used as an animal model of MODY.