Model Introduction
The MKR mouse is a transgenic animal model of Type 2 diabetes mellitus (T2DM) developed by Fernández et al. The core principle of this model is the overexpression of an inactive insulin-like growth factor-1 receptor (IGF-1 receptor) in skeletal muscle. These inactive receptors bind with endogenous IGF-1 receptors and insulin receptors to form hybrid receptors. This mechanism interferes with the normal signal transduction functions of the related receptors, leading to significant systemic insulin resistance.
Research Applications
This model is primarily used to simulate the occurrence and development of Type 2 diabetes, reveal the pathogenesis of insulin resistance, and screen or evaluate therapeutic drugs for diabetes (such as the study of PPAR-γ agonist efficacy mentioned in reference materials).
Key Points of Experimental Design
- Model Source and Background: Developed using transgenic technology; classified as a genetically engineered diabetes animal model.
- Disease Timeline:
- 2 weeks of age: Significant hyperinsulinemia appears.
- After 5 weeks of age: Fasting and postprandial blood glucose levels begin to rise gradually.
- 7–12 weeks of age: Significant impaired glucose tolerance (IGT) is observed.
- Drug Intervention Reference: Experimental records show that treatment with the PPAR-γ agonist WY14,643 can correct metabolic abnormalities in this model.
Key Monitoring Indicators
- Serum Biochemical Indicators: Insulin levels (to evaluate hyperinsulinemia), fasting blood glucose, postprandial blood glucose.
- Glucose Metabolism Indicators: Glucose tolerance test (to evaluate the degree of impaired glucose tolerance).
- Molecular Mechanism Indicators: Functional status of IGF-1 receptors and insulin receptors, and the formation of hybrid receptors (no specific detection parameters recorded based on existing data).
