JAX Notes July 01, 2008

BKS.Cg-m +/+ Leprdb/J (000642), one of the most widely used diabetes models at JAX

Who would have thought that a black mouse with a chance mutation would one day become one of the most requested mice in diabetes and obesity research? Such is the case with BKS.Cg- Dock7m +/+ Leprdb/J (000642), a JAX® Mice strain harboring the spontaneous diabetes mutation (db) in the leptin receptor (Lepr) gene. The JAX® Mice Database lists over 300 journal articles with this mouse as a main character. It has played a key role in many research areas, including type 2 diabetes, obesity, endocrine defects, fertility, immunodeficiency, metabolism, cardiovascular, thermoregulation and wound healing. Its popularity as a research tool has resulted in its extensive characterization.


Because Leprdb homozygotes are sterile, we have incorporated the “misty” coat color mutation (m; Dock7m) into our Leprdb colonies to allow genotyping offspring by their appearance.  In strain 000642, the db and m alleles are maintained in repulsion – that is, with one mutant allele on each of the two copies of mouse chromosome 4.  In this genetic arrangement, homozygous db/db mice (genotype: + db/+ db) are black and fat (not shown), heterozygotes (m +/ + db) used for breeding are black and lean black (upper left), and homozygous Lepr wild-types (m +/m +) are misty (lower right).

Some of this strain’s more notable features include the following:

  • Diabetes phenotypes: transient hyperinsulinemia, insulin resistance, chronic hyperglycemia, glucose intolerance, abnormal islet morphology (Hummel et al. 1966. Science 153:1127-8; Uchida et al. 2005. Nat Med 11:175-82; Yamauchi et al. 2007. Nat Med 13: 332-9); peripheral neuropathy (Raizada et al. 1980. J Biol Chem 255:9149-55; Robertson and Smith. 1980. Diabetes 29:60-7)
  • Exogenous insulin fails to control blood glucose levels (Robertson and Smith. 1980. Diabetes 29:60-7)
  • Renal defects: increased creatinine clearance, decreased albumin secretion (Wendt et al. 2003. Am J Pathol 162:1123-37)
  • Obese by 3-4 weeks of age (Hummel et al. 1966. Science 153:1127-8; Greer. 2006. Am J Physiol Heart Circ Physiol 290 H146-53)
  • Abnormal lipid levels: high HDL, LDL, VLDL, and triglyceride levels (Nishina et al. 1994. Metabolism 43:549-53)
  • Polyphagic (Uchida et al. 2005. Nat Med 11:175-82)
  • Severe liver steatosis (Kanda et al. 2006. J Clin Invest 116:1494-505)
  • Low body temperature (Trayhurn. 1979. Pflugers Arch 380:227-32; Uchida et al. 2005. Nat Med 11:175-82)
  • Increased gluconeogenic enzyme activity (Leiter et al. 1979. In Vitro 15:507-21)
  • Cardiovascular defects (Greer et al. 2006. Am J Physiol Heart Circ Physiol 290:H146-53; How et al. Diabetes 55:466-73)
  • Reproductive defects: sterile, low uterine and ovarian weights, low ovarian hormone production and hypercytolipidemia in follicular granulosa and endometrial epithelial tissue layers (Garris. 2004. Tissue Cell 36:19-28)
  • Increased metabolic efficiency (Trayhurn. 1979. Pflugers Arch 380:227-32)
  • Delayed wound healing (Werner et al. 1994. J Invest Dermatol 103:469-73; Brem et al. 2007. Exp Gerontol 42:523-31)