Strain Name: |
B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ |
|---|---|
Stock Number: |
006860 |
Availability: | Repository- Live |
General Terms and Conditions |
| Strain Common Names | B6-Akita, B2R; B6-B2R, Akita; |
| Genes & Alleles | Bdkrb2; Bdkrb2tm1Jfh; Ins2; Ins2Akita; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Spontaneous Mutation Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S7 Donating Investigator Masao Kakoki, University of North Carolina at Chapel H Generation N9F?+N1F1 (11-DEC-07) Strain Description
Mice homozygous for the targeted mutation and heterozygous for the Akita spontaneous mutation are viable and fertile. Similar to mice only heterozygous for the Akita 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.
Strain Development
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.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Bdkrb2tm1Jfh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, J Fred Hess | ||
| Common Name(s) | B2-; B2R-; BdkrB2; Bk B2R-; Bk2r-; rB2 <->; | ||
| Mutation Made By | J. Hess, Merck Research Laboratories | ||
| Strain of Origin | 129S7/SvEvBrd-Hprt1 | ||
| ES Cell Line Name | AB2.1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt1 | ||
| 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; DKFZp686O088; kinin B2; | ||
| 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. [MGI Ref ID J:25953] | ||
| Allele Symbol | Ins2Akita | ||
| Allele Name | Akita | ||
| Common Name(s) | Ins2C96Y; Ins2Mody; Mody; Mody4; | ||
| Strain of Origin | C57BL/6 | ||
| Gene Symbol and Name | Ins2, insulin II | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | AA986540; ILPR; IRDN; Ins-2; InsII; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4; | ||
| Molecular Note | In the mutant allele a transition from G to A at nucleotide 1907 disrupted 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). 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. [MGI Ref ID J:51935] | ||
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Bdkrb2tm1Jfh
Colony Maintenance
| Diet Information | LabDiet® 5K52/5K67 |
|---|
Related Strains
Strains carrying Bdkrb2tm1Jfh allele
002641 B6;129S7-Bdkrb2tm1Jfh/J View Strains carrying Bdkrb2tm1Jfh (1 strain)
006580 B6.Cg-Ins2Akita Ldlrtm1Her/J 004369 B6.Cg-Rag1tm1Mom Ins2Akita/J 003548 C57BL/6-Ins2Akita/J 007562 D2.B6-Ins2Akita/MatbJ 006867 FVB.B6-Ins2Akita/MlnJ
Additional Web Information
Congenic Nomenclature
Animal Health Reports
Room Number FGB29
Research Applications
This mouse can be used to support research in many areas including:
Ins2 relatedApoptosis Research
Cancer Research
Growth Factors/Receptors/Cytokines (Osteoporosis)
Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM) (MODY, mature onset diabetes of the young)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Inflammation
Internal/Organ Research
Kidney Defects
Bdkrb2tm1Jfh relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Ins2Akita relatedCardiovascular Research
Hypertension (diet-induced)
Immunology and Inflammation Research
Inflammation
Cell Biology Research
Protein Processing
Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Islet Transplantation Studies
Type 1 Diabetes (IDDM) (MODY, mature onset diabetes of the young)
Endocrine Deficiency Research
Pancreas Defects
References
Selected Reference(s)
Additional ReferencesKakoki M; Kizer CM; Yi X; Takahashi N; Kim HS; Bagnell CR; Edgell CJ; Maeda N; Jennette JC; Smithies O. 2006. Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors. J Clin Invest 116(5):1302-9. [PubMed: 16604193] [MGI Ref ID J:108948]
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; Takahashi N; Jennette JC; Smithies O. 2004. Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor. Proc Natl Acad Sci U S A 101(36):13302-5. [PubMed: 15326315] [MGI Ref ID J:92403]
Price and Supply Information
| Strain Name: | B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ |
| Stock Number: | 006860 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Type 1 Diabetes Repository collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license.
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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.Ordering and Purchasing Information
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