BKS.Cg-m +/+ Leprdb/J (000642), One of the Most Widely-used Diabetes Models at JAX

JAX® NOTES Issue 510, Summer 2008

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-m +/+ 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.

(Stock Number 000642)

Since Leprdb homozygotes are sterile, we have incorporated the misty coat color mutation (m) into our BKS.Cg-m +/+ Leprdb/J colonies. Homozygotes, with the coupling double heterozygous genotype (m Leprdb/+ +), are black (upper left); heterozygotes, with the repulsion double heterozygous genotype (m +/+ Leprdb), are misty (lower right) and used for breeding.

Some of its more notable features include the following:

  • Diabetes phenotypes: hyperinsulinemia, insulin resistance, 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 three to four 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)

To find out more, start with the JAX® Mice Database (000642), or the Mouse Phenome Database. Maybe you’ll decide that this is the mouse you’ve been looking for, or maybe you'll find another JAX® Mice strain that is more appropriate. In either case, you can order JAX® Mice by contacting Customer Service at orderquest@jax.org, 1-800-422-6423, or 1-207-288-5845.