疾病动物模型,2型糖尿病 z-bio 2021-03-11 370

　　[Modeling mechanism] Type 2 diabetes is genetically inherited, and there are many mechanisms involved in the pathogenesis. In order to clarify the role of a single gene in the pathogenesis of type 2 diabetes, a series of type 2 diabetes animal models can be replicated by means of gene knockout or gene overexpression.

　　1. GK/IRS-1 double gene knockout mice The mouse glucokinase gene exon is replaced with neo-mycin resistance gene to make the target vector heterozygous into normal mice, and GK-/- Mice. IRS-1 -/- mice showed insulin resistance, but due to the compensatory proliferation of β cells, insulin secretion increased, and glucose tolerance was normal. Mice with decreased β-cell-specific GK expression showed mild impaired glucose tolerance. The GK/IRS-1 double gene knockout mice produced by the hybridization of the two have impaired glucose tolerance, low glucose sensitivity of hepatocytes and pancreatic islet β cells, and exhibit symptoms of type 2 diabetes.

　　2. IR +/-/IRS-1 +/- double gene knockout heterozygous mice IR+/- and IRS-1 +/- single gene knockout heterozygous mice have no obvious clinical symptoms. However, 40% of the IR +/- /IRS-1 +/- double gene knockout heterozygous mice developed overt diabetes 4-6 months later, accompanied by hyperinsulinemia and pancreatic β-cell proliferation. The animal model of type 2 diabetes has obvious insulin resistance.

　　3. MKR transgenic mice MKR mice with a lack of function of the skeletal muscle insulin-like growth factor-1 (IGF-1) receptor, due to the formation of hybrid receptors, show loss of function of the insulin receptor. MKR mice have a significant increase in blood glucose from 3 weeks of birth, and show significant insulin resistance, hyperglycemia, pancreatic B cell dysfunction, and lipid metabolism disorders after 5 weeks.

　　【Features of the model】GK+/-/IRS-1 -/- mice have impaired glucose tolerance and decreased glucose sensitivity of pancreatic β-cells and hepatocytes. The use of this type of model for diabetes research is highly scientific. IR +/- /IRS-1 +/- double gene knockout heterozygous mice are type 2 diabetes animal models. The MKR transgenic mouse model has fast onset, simple application and high survival rate.

　　[Model Evaluation and Application] GK/IRS-1 double gene knockout mice are similar to humans with maturity onset diabetes of the young (MODY) and can be used as MODY animal models. Both IR+/-/IRS-1+/- double gene knockout heterozygous mice and MKR transgenic mice can be used to study the pathogenesis and prevention methods of type 2 diabetes.