Mice homozygous for this targeted mutation of the bradykinin receptor, beta 2 (Bdkrb2) gene and heterozygous for the Akita spontaneous mutation of the insulin 2 (Ins2) gene (Ins2Akita) are viable and fertile. They are extremely diabetic, underweight, hyperphagic, polyuric, and have severe kidney, skeletal, and testicular defects. essentially no subcutaneous fat, and a significantly reduced lifespan. This strain may be used to research the kallikrein-kinin system, specifically the role of bradykinin B2 receptor in diabetes, oxidative stress, mitochondrial DNA damage, apoptosis, kidney morphology and function, and other senescence-associated phenotypes.
Dr. Masao Kakoki, University of North Carolina at Chapel H
Genetic Background | Generation |
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000664 C57BL/6J |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Bdkrb2 | bradykinin receptor, beta 2 |
Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Ins2 | insulin II |
Mice homozygous for the targeted mutation and heterozygous for the Ins2Akita spontaneous mutation are viable and fertile. Similar to mice only heterozygous for the Ins2Akita mutation, the double mutant mice are severely diabetic: their body weights are 70% of wildtype, they consume over 3-fold the normal amount of food, and their urinary output is approximately 20-fold more than that of wildtype mice. Double mutant mice have markedly enlarged kidneys. Urinary albumin excretion in double mutants is almost 4-fold that of either single mutant, and double mutants experience more severe nephropathy than mice that are heterozygous for the Akita mutation alone. Megsin and nephrin expression is markedly increased in double mutant mice when compared to wildtype or to mice with either single mutation alone. By 12 months of age, double mutant mice experience hair loss due to a reduction in hair follicle numbers and thinning of the dermis. Double mutants have essentially no subcutaneous fat, severe kyphosis, reduced bone density, osteoporosis, testicular atrophy, lipofuscin accumulation in the renal proximal tubule and testicular Leydig cells, increased apoptosis in the testicular seminiferous tubules and intestinal villi, and a significantly reduced lifespan.
This model is useful for studying the kallikrein-kinin system, specifically the role of bradykinin B2 receptor in diabetes, oxidative stress, mitochondrial DNA damage, apoptosis, morphological and functional kidney changes, and other senescence-associated phenotypes.
Dr. Oliver Smithies laboratory backcrossed Stock No. 002641 B6;129S7-Bdkrb2tm1Jfh/J mice to C57BL/6J (Stock No. 000664) for an additional 6 generations prior to mating to Stock No. 003548 C57BL/6-Ins2Akita/J. In 2007, The Jackson Laboratory received C57BL/6 congenic males homozygous for the Bdkrb2tm1Jfh mutation at N9F? and mated them to heterozygous females from Stock No. 003548 C57BL/6-Ins2Akita/J. The strain has been maintained subsequently by brother x sister matings.
Genetic quality control completed at The Jackson Laboratory indicates that there is 129 genetic contamination on chromosomes 3, 4, 6, 11, 15 and 17 (006860 SNP's marker data)
Allele Name | targeted mutation 1, J Fred Hess |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | B2-; B2-KO; B2R-; BdkrB2; Bk B2R-; Bk2r-; rB2 - |
Gene Symbol and Name | Bdkrb2, bradykinin receptor, beta 2 |
Gene Synonym(s) | |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 12 |
Molecular Note | A neomycin selection cassette replaced the entire coding sequences of the gene. Binding assays on membranes prepared from ileum tissue of homozygous mice confirmed that no functional protein is produced from this allele. |
Mutations Made By | Dr. J. Hess, Merck Research Laboratories |
Allele Name | Akita |
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Allele Type | Spontaneous |
Allele Synonym(s) | Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4 |
Gene Symbol and Name | Ins2, insulin II |
Gene Synonym(s) | |
Strain of Origin | C57BL/6NSlc |
Chromosome | 7 |
Molecular Note | In the mutant allele a transition from G-to-A at coding nucleotide 287 disrupts an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC) (p.C96Y). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin. |
When using the B6-B2R, Akita mouse strain in a publication, please cite the originating article(s) and include JAX stock #006860 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Ins2<Akita>,Heterozygous for Bdkrb2<tm1Jfh> |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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