Publications report that mice homozygous for targeted mutations in the tandem bradykinin B1 and B2 receptors, commonly referred to as B1RB2R -/-, are viable, fertile and display no major defects. At 4 months of age, non-manipulated B1RB2R -/- mice exhibited no significant differences in blood pressure or kidney function when compared to mice deficient only in the B2 receptor. Fasted B1RB2R -/- mice exhibited significantly lower levels of plasma nitrite/nitrate compared to Bdkrb2 deficient mice.
Post-ischemic B1RB2R -/- mice exhibited significantly higher plasma levels of urea nitrogen and creatinine, higher levels of oxidative nuclear and mitochondrial DNA modification, and increased rates of apoptosis and mortality than either wildtype or Bdkrb2 deficient mice. Histological evaluation of the kidney showed that post ischemic B1RB2R -/- mice exhibit more severe histological changes in the renal proximal tubules than either wildtype or Bdkrb2 deficient mice (Kakoki et al, 2007). The Ins2Akita mutation was introduced by cross with the B6- Ins2Akita stock to assess the effect of chronic diabetes on complications development in The Jackson Laboratory vivarium. In B1RB2R -/- male but not female mice, mean albumin/creatinine ratio (ACR) in urine was modestly elevated at 25 weeks of age. However, no significant renal histopathologic lesion development distinguished diabetic Ins2Akita and normoglycemic non-Akita B1RB2R -/- mice at 6 months of age.
This doubly-targeted Bdkrb1/Bdkrb2 stock is useful for studying the kallikrein-kinin system, specifically the role of bradykinin B1 receptor and bradykinin B2 receptor in oxidative stress, mitochondrial DNA damage, apoptosis, morphological and functional kidney changes, and other senescence-associated phenotypes.