Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Background Strain C57BL/6 Generation ?+F1pN1 Generation Definitions   Donating Investigator Masao Kakoki,   University of North Carolina at Chapel H

Appearance
black
Related Genotype: a/a

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.

Control Information

	Control
	006860 B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Bdkrb2

006860	B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ
002641	B6;129S7-Bdkrb2tm1Jfh/J

View Strains carrying other alleles of Bdkrb2     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Bdkrb2/Bdkrb1^tm1Mki/Bdkrb2/Bdkrb1^tm1Mki

        involves: C57BL/6J

• mortality/aging
• increased sensitivity to induced morbidity/mortality
  • increased mortality following renal ischemia/reperfusion procedure (8 of 13) compared to wild-type (0 of 10), sham controls (0 of 10) and Bdkrb2^tm1Jfh homozygotes (1 of 8)   (MGI Ref ID J:121339)
• renal/urinary system phenotype
• abnormal kidney morphology
  • in the kidney of postischimic mice there is more oxidative nuclear and mitochondrial DNA modification than in wild-type and Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)
  • apoptosis rates are increased in postischemic mice compared to in wild-type and Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)
• • abnormal proximal convoluted tubule morphology
    • postischimic mice have more severe histologial changes in renal proximal tubules than in wild-type and Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)
• homeostasis/metabolism phenotype
• decreased blood urea nitrogen level
  • fasting plasma nitrite/nitrate levels are decreased to a greater degree than in Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)
• increased blood urea nitrogen level
  • postischimic mice have increased plasma urea nitrogen compared to wild-type and Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)
• increased circulating creatinine level
  • postischimic mice have increased plasma creatinine compared to wild-type and Bdkrb2^tm1Jfh homozygotes   (MGI Ref ID J:121339)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Apoptosis Research

Cell Biology Research
DNA Damage Response

Immunology and Inflammation Research
Inflammation

Internal/Organ Research
Kidney Defects

Research Tools
Apoptosis Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bdkrb2/Bdkrb1tm1Mki
Allele Name		targeted mutation 1, Masao Kakoki
Allele Type		Targeted (knock-out)
Common Name(s)		B1RB2R-null; Bdkrb1-/Bdkrb2-;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Bdkrb2, bradykinin receptor, beta 2
Chromosome		12
Gene Common Name(s)		B(2); B2; B2BKR; B2BRA; B2R; BK-2; BK2; BK2R; BKR2; BRB2; kinin B2;
Associated Marker Note		Affected-Count: 1Af1-Gene: MGI:88144
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. [MGI Ref ID J:121339]
Gene Symbol and Name		Bdkrb1, bradykinin receptor, beta 1
Chromosome		12
Gene Common Name(s)		B1BKR; B1R; BKB1R; BKR; BKR1; BRADYB1; Bdkrb; kinin B1;

Genotyping

Genotyping Information

Genotyping Protocols

Bdkrb2/Bdkrb1^tm1Mki, Standard PCR
Nnt^C57BL/6J, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Kakoki M; McGarrah RW; Kim HS; Smithies O. 2007. Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury. Proc Natl Acad Sci U S A 104(18):7576-81. [PubMed: 17452647]  [MGI Ref ID J:121339]

Kakoki M; Sullivan KA; Backus C; Hayes JM; Oh SS; Hua K; Gasim AM; Tomita H; Grant R; Nossov SB; Kim HS; Jennette JC; Feldman EL; Smithies O. 2010. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A 107(22):10190-5. [PubMed: 20479236]  [MGI Ref ID J:161075]

Wende AR; Soto J; Olsen CD; Pires KM; Schell JC; Larrieu-Lahargue F; Litwin SE; Kakoki M; Takahashi N; Smithies O; Abel ED. 2010. Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice. Endocrinology :. [PubMed: 20501666]  [MGI Ref ID J:161074]

Bdkrb2/Bdkrb1^tm1Mki related

Kakoki M; McGarrah RW; Kim HS; Smithies O. 2007. Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury. Proc Natl Acad Sci U S A 104(18):7576-81. [PubMed: 17452647]  [MGI Ref ID J:121339]

Kakoki M; Sullivan KA; Backus C; Hayes JM; Oh SS; Hua K; Gasim AM; Tomita H; Grant R; Nossov SB; Kim HS; Jennette JC; Feldman EL; Smithies O. 2010. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A 107(22):10190-5. [PubMed: 20479236]  [MGI Ref ID J:161075]

Wende AR; Soto J; Olsen CD; Pires KM; Schell JC; Larrieu-Lahargue F; Litwin SE; Kakoki M; Takahashi N; Smithies O; Abel ED. 2010. Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice. Endocrinology :. [PubMed: 20501666]  [MGI Ref ID J:161074]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Type 1 Diabetes Repository collection.

Control Information

	Control
	006860 B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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