C57BL/6-Del(12Bdkrb2-Bdkrb1)1Mki/J

Stock number: 012371
Product name: NOD.B1RB2R-/-
Research areas: Apoptosis Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Bradykinin receptor, beta 1(Bdkrb1) and Bradykinin receptor, beta 2 (Bdkrb2) deficient mice, commonly referred to as B1RB2R-/-, exhibit significant post ischemic DNA damage, apoptosis, and kidney changes. This strain may be useful for studying the kallikrein-kinin system, specifically the role of bradykinin B1 and B2 receptors in oxidative stress, mitochondrial DNA damage, apoptosis, kidney morphology and function, and other senescence-associated phenotypes.

Detailed description

Mice homozygous for the targeted mutation, commonly referred to as B1RB2R -/-, are viable, fertile and display no major defects. At 4 months of age non-manipulated B1RB2R -/- mice exhibit no significant differences in blood pressure or kidney function when compared to Bdkrb2 deficient mice (Stock No. 006860). Fasted B1RB2R -/- mice exhibit significantly lower levels of plasma nitrite/nitrate compared to Bdkrb2 deficient mice.

Post-ischemic B1RB2R -/- mice exhibit 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 indicates 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).

This Bdkrb1/Bdkrb2 targeted mutation 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.

Development

A construct, containing a floxed neomycin resistance cassette replaced exon 3 of the bradykinin receptor, beta 2 and the bradykinin receptor, beta 1 exon, was transfected into C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cell clones were injected into C57BL/6 blastocysts. Upon arrival at The Jackson Laboratory this strain has been mated to C57BL/6J (Stock No. 000664) prior to breeding to homozygosity. SNP testing confirms genetic background is C57BL/6. The T1DR received this strain in 2010.

Allele

Symbol: Del(12Bdkrb2-Bdkrb1)1Mki
Name: deletion, Chr 12, Masao Kakoki 1
MGI accession ID: MGI:3710158
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Del(12Bdkrb2-Bdkrb1)1Mki
Marker name: deletion, Chr 12, Masao Kakoki 1
Chromosome: 12
Strain of origin: C57BL/6J
Molecular note: A targeting vector was designed to replace bradykinin receptor, beta 2 exon 3 and the bradykinin receptor, beta 1 exon with a floxed neomycin resistance cassette.