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
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|
|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)||B(2); B2; B2BKR; B2BRA; B2R; BK-2; BK2; BK2R; BKR2; BRB2; kinin B2|
|Strain of Origin||129S7/SvEvBrd-Hprt |
|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 Synonym(s)||Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4|
|Gene Symbol and Name||Ins2, insulin II|
|Gene Synonym(s)||AA986540; CP-II; IDDM; IDDM1; IDDM2; ILPR; IRDN; Ins-2; Ins-2; InsII; MODY10; Mody; Mody; Mody4; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4|
|Strain of Origin||C57BL/6NSlc|
|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.|
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.
|Heterozygous or Wild-type for Ins2<Akita>,Heterozygous for Bdkrb2<tm1Jfh>|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.
"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.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
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.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
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.