Overview

Also Known As: B6-Akita, B2R, B6-B2R, Akita

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 (Ins2^Akita) 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.

Donating Investigator

Dr. Masao Kakoki, University of North Carolina at Chapel H

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Ins2^Akita

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ins2	insulin II

Bdkrb2^tm1Jfh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Bdkrb2	bradykinin receptor, beta 2

View Genetics

Research Applications

Diabetes and Obesity Research
Cell Biology Research
Endocrine Deficiency Research
Cancer Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Cardiovascular Research
Apoptosis Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Mice homozygous for the targeted mutation and heterozygous for the Ins2^Akita spontaneous mutation are viable and fertile. Similar to mice only heterozygous for the Ins2^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.

Development

Dr. Oliver Smithies laboratory backcrossed Stock No. 002641 B6;129S7-Bdkrb2^tm1Jfh/J mice to C57BL/6J (Stock No. 000664) for an additional 6 generations prior to mating to Stock No. 003548 C57BL/6-Ins2^Akita/J. In 2007, The Jackson Laboratory received C57BL/6 congenic males homozygous for the Bdkrb2^tm1Jfh mutation at N9F? and mated them to heterozygous females from Stock No. 003548 C57BL/6-Ins2^Akita/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)

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Kakoki 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):1302-9PubMed: 16604193 MGI: 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):7576-81PubMed: 17452647 MGI: 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):13302-5PubMed: 15326315 MGI: J:92403

View All References

Genetics

Ins2^Akita

Allele Symbol: Ins2^Akita

Allele Name	Akita
Allele Type	Spontaneous
Allele Synonym(s)	Akita; Ins2^Akita
Gene Symbol and Name	Ins2, insulin II
Gene Synonym(s)	expressed sequence AA986540; Mody; Ins-2; Mody4; Mody; MODY10; AA986540; maturity onset diabetes of the young 4; ILPR; Ins-2; InsII; IRDN; maturity onset diabetes of the young; Mody4; IDDM1; IDDM2; IDDM; CP-II
Strain of Origin	C57BL/6NSlc
Chromosome	7
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.

Bdkrb2^tm1Jfh

Allele Symbol: Bdkrb2^tm1Jfh

Allele Name	targeted mutation 1, J Fred Hess
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, J Fred Hess; Bdkrb2^tm1Jfh
Gene Symbol and Name	Bdkrb2, bradykinin receptor, beta 2
Gene Synonym(s)	B(2); B2; B2BKR; B2BRA; B2R; BK-2; BK2; BK2R; BRB2; kinin B2; BKR2
Strain of Origin	129S7/SvEvBrd-Hprt^b-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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Ins2^Akita related

Diabetes and Obesity Research
- Islet Transplantation Studies
- Hyperglycemia
- Hypoinsulinemia
- Insulin Receptors and Growth Factors
- Type 1 Diabetes (IDDM)
  - MODY, mature onset diabetes of the young
- Impaired Insulin Processing
Cell Biology Research
- Protein Processing
Endocrine Deficiency Research
- Pancreas Defects

Cancer Research
- Growth Factors/Receptors/Cytokines
  - Osteoporosis
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - Type 1 Diabetes
- Inflammation
Diabetes and Obesity Research
- Hyperglycemia
- Impaired Insulin Processing
- Hypoinsulinemia
- Insulin Receptors and Growth Factors
- Type 1 Diabetes (IDDM)
  - MODY, mature onset diabetes of the young
Internal/Organ Research
- Skeleton
  - Bone
- Kidney Defects
Apoptosis Research

Genotype: Bdkrb2^tm1Jfh related

Immunology, Inflammation and Autoimmunity Research
- Inflammation
Cardiovascular Research
- Hypertension
  - diet-induced

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Bdkrb2^tm1Jfh/Bdkrb2^tm1Jfh Ins2^Akita/Ins2⁺
B6.Cg-Ins2 Bdkrb2

adipose tissue phenotype

decreased subcutaneous adipose tissue amount
- mutants have almost no subcutaneous fat

reproductive system phenotype

abnormal Leydig cell morphology
- double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age

abnormal seminiferous tubule morphology
- double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age

abnormal spermatogonia morphology
- in double mutant males, severe loss of spermatogonia is observed and atrophy of spermatic cords is prevalent at 12 months of age

skeleton phenotype

decreased bone mineral density
- double mutants have significantly reduced bone density compared to wild-type or single mutant mice

kyphosis
- double mutants exhibit marked kyphosis

cellular phenotype

abnormal mitochondrial chromosome morphology
- mutants display increased mitochondrial DNA damage compared to single mutants or wild-type mice at 12 months of age

abnormal spermatogonia morphology
- in double mutant males, severe loss of spermatogonia is observed and atrophy of spermatic cords is prevalent at 12 months of age

digestive/alimentary phenotype

abnormal intestinal epithelium morphology
- intestinal villi in mutants have a greater frequency of apoptotic cells

endocrine/exocrine gland phenotype

abnormal Leydig cell morphology
- double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age

abnormal seminiferous tubule morphology
- double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age

integument phenotype

alopecia
- most mutants show significant alopecia by 12 months of age

decreased subcutaneous adipose tissue amount
- mutants have almost no subcutaneous fat

mortality/aging

premature death
- mice have much shorter lifespan than wild-type; 909 days (wt) vs 246 days (mutant)

References

Kakoki 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):1302-9PubMed: 16604193 MGI: 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):7576-81PubMed: 17452647 MGI: 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):13302-5PubMed: 15326315 MGI: J:92403

Additional - Bdkrb2^tm1Jfh related

Additional - Ins2^Akita related

Technical Support

Contact Technical Support

Genotyping Protocols
- Restriction Enzyme Digest: Ins2^Akita
- End Point Analysis: Ins2^Akita
- MELT: Bdkrb2^tm1Jfh
- Standard PCR: Bdkrb2^tm1Jfh
- Genotyping resources and troubleshooting
Appearance
- black
  Related Genotype: a/a
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wild-type for Ins2<Akita>,Heterozygous for Bdkrb2<tm1Jfh>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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General Terms and Conditions

Questions about Terms of Use

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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.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As: B6-Akita, B2R, B6-B2R, Akita

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ins2Akita

Allele Symbol: Ins2Akita

Bdkrb2tm1Jfh

Allele Symbol: Bdkrb2tm1Jfh

Disease Terms

Research Areas By Genotype

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

Genotype: Ins2Akita related

Genotype: Bdkrb2tm1Jfh related

Mammalian Phenotype Terms by Genotype

Genotype: Bdkrb2tm1Jfh/Bdkrb2tm1Jfh Ins2Akita/Ins2+B6.Cg-Ins2 Bdkrb2

adipose tissue phenotype

reproductive system phenotype

skeleton phenotype

cellular phenotype

digestive/alimentary phenotype

endocrine/exocrine gland phenotype

integument phenotype

mortality/aging

References

Additional - Bdkrb2tm1Jfh related

Additional - Ins2Akita related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ins2^Akita

Allele Symbol: Ins2^Akita

Bdkrb2^tm1Jfh

Allele Symbol: Bdkrb2^tm1Jfh

Genotype: Ins2^Akita related

Genotype: Bdkrb2^tm1Jfh related

Genotype: Bdkrb2^tm1Jfh/Bdkrb2^tm1Jfh Ins2^Akita/Ins2⁺
B6.Cg-Ins2 Bdkrb2

Additional - Bdkrb2^tm1Jfh related

Additional - Ins2^Akita related