[Animal modeling] - KK mice with hereditary diabetes

  The KK mouse was successfully cultivated in 1957 by Japan's Konteng family using the original Japanese mouse (also known as the "twenty day mouse"). In 1962, Nakamura reported that KK mice had similar properties to adult obese diabetes, which attracted the attention of the medical community (the Chinese Academy of Medical Sciences maintains KK mouse strains). KK mice fed with commercially available solid feed rarely exhibit symptoms of urinary glucose and hyperglycemia, but only exhibit diabetic traits in glucose tolerance tests (non obese KK mice). Animals may develop obesity, often accompanied by hyperinsulinemia and hyperglycemia (obese KK mice), by feeding them high-energy feed, administering gold sulfur glucose, or introducing obesity genes (AY). In obese KK mice, the sexual changes of diabetes are very similar to those of adults with diabetes, that is, both insulin and blood sugar in the blood are increased, and the phenomenon of degranulation of pancreatic B cells, as well as the proliferation of glomerular mesangial cells and hypertrophy of basement membrane are the main changes.

  KK mice not only exhibit an increase in fat synthesis in their liver and adipose tissue, but also a decrease in insulin sensitivity involved in glucose metabolism in adipose and muscle tissues, which is most evident in obese KK mice. Excessive fat synthesis can lead to obesity, while decreased insulin sensitivity in peripheral tissues can lead to hyperglycemia. The regulatory mechanism of fat differentiation is also disrupted, and fasting rarely leads to an increase in free fatty acids in the blood.

  【 Result Analysis 】 Compared with normal C57BL mice, KK mice have lower glucose tolerance, insulin and adrenaline sensitivity. In the first generation of C57BL and KK hybrid mice, these indicators are between the two parents. The change of diabetes in KK mice is controlled by multiple genes. Therefore, the F1 mice can be used separately to obtain diabetes animals of different degrees, which may correspond to the diversity of human diabetes. Therefore, as a human diabetes model, KK mice have different uses from ob/ob, db/db mouse mutants.