Strain Name:

B6.Cg-Ins2Akita Bdkrb2tm1Jfh/SmiJ

Stock Number:


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Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
Common Names: 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 (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.


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 Congenic; Spontaneous Mutation; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain 129S7
Generation Definitions
Donating InvestigatorDr. Masao Kakoki,   University of North Carolina at Chapel H

Related Genotype: a/a

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)

Control Information

   000664 C57BL/6J
  Considerations for Choosing Controls

Related Strains

Strains carrying   Bdkrb2tm1Jfh allele
002641   B6;129S7-Bdkrb2tm1Jfh/J
View Strains carrying   Bdkrb2tm1Jfh     (1 strain)

View Strains carrying   Ins2Akita     (11 strains)

View Strains carrying other alleles of Ins2     (7 strains)


Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Diabetes Mellitus, Insulin-Dependent, 2   (INS)
Diabetes Mellitus, Permanent Neonatal; PNDM   (INS)
Hyperproinsulinemia   (INS)
Maturity-Onset Diabetes of the Young, Type 10; MODY10   (INS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Bdkrb2tm1Jfh/Bdkrb2tm1Jfh Ins2Akita/Ins2+

        B6.Cg-Ins2Akita Bdkrb2tm1Jfh
  • mortality/aging
  • premature death
    • mice have much shorter lifespan than wild-type; 909 days (wt) vs 246 days (mutant)   (MGI Ref ID J:108948)
  • 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   (MGI Ref ID J:108948)
  • endocrine/exocrine gland phenotype
  • abnormal seminiferous tubule morphology
    • double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age   (MGI Ref ID J:108948)
    • abnormal Leydig cell morphology
      • double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age   (MGI Ref ID J:108948)
  • reproductive system phenotype
  • abnormal seminiferous tubule morphology
    • double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age   (MGI Ref ID J:108948)
    • abnormal Leydig cell morphology
      • double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age   (MGI Ref ID J:108948)
  • 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   (MGI Ref ID J:108948)
  • digestive/alimentary phenotype
  • abnormal intestinal epithelium morphology
    • intestinal villi in mutants have a greater frequency of apoptotic cells   (MGI Ref ID J:108948)
  • adipose tissue phenotype
  • decreased subcutaneous adipose tissue amount
    • mutants have almost no subcutaneous fat   (MGI Ref ID J:108948)
  • skeleton phenotype
  • decreased bone mineral density
    • double mutants have significantly reduced bone density compared to wild-type or single mutant mice   (MGI Ref ID J:108948)
  • kyphosis
    • double mutants exhibit marked kyphosis   (MGI Ref ID J:108948)
  • integument phenotype
  • alopecia
    • most mutants show significant alopecia by 12 months of age   (MGI Ref ID J:108948)
  • decreased subcutaneous adipose tissue amount
    • mutants have almost no subcutaneous fat   (MGI Ref ID J:108948)
View Research Applications

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

Apoptosis Research

Cancer Research
Growth Factors/Receptors/Cytokines

Diabetes and Obesity Research
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)
      MODY, mature onset diabetes of the young

Immunology, Inflammation and Autoimmunity Research
      Type 1 Diabetes

Internal/Organ Research
Kidney Defects

Bdkrb2tm1Jfh related

Cardiovascular Research

Immunology, Inflammation and Autoimmunity Research

Ins2Akita related

Cell Biology Research
Protein Processing

Diabetes and Obesity Research
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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol Bdkrb2tm1Jfh
Allele Name targeted mutation 1, J Fred Hess
Allele Type Targeted (Null/Knockout)
Common Name(s) B2-; B2-KO; B2R-; BdkrB2; Bk B2R-; Bk2r-; rB2 -;
Mutation Made ByDr. J. Hess,   Merck Research Laboratories
Strain of Origin129S7/SvEvBrd-Hprt
ES Cell Line NameAB2.1
ES Cell Line Strain129S7/SvEvBrd-Hprt
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;
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
Allele Type Spontaneous
Common Name(s) Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4;
Strain of OriginC57BL/6NSlc
Gene Symbol and Name Ins2, insulin II
Chromosome 7
Gene Common Name(s) AA986540; IDDM; IDDM1; IDDM2; ILPR; IRDN; Ins-2; InsII; MODY10; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4;
General Note Phenotypic Similarity to Human Syndrome: Type 1 Diabetic Macrovascular Disease (J:174983)
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]


Genotyping Information

Genotyping Protocols

Bdkrb2tm1Jfh, MELT
Bdkrb2tm1Jfh, Standard PCR
Ins2Akita, End Point Analysis
Ins2Akita, Restriction Enzyme Digest

Helpful Links

Genotyping resources and troubleshooting


References provided by MGI

Selected Reference(s)

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):1302-9. [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]

Additional References

Bdkrb2tm1Jfh related

Abadir PM; Carey RM; Siragy HM. 2003. Angiotensin AT2 receptors directly stimulate renal nitric oxide in bradykinin B2-receptor-null mice. Hypertension 42(4):600-4. [PubMed: 12953015]  [MGI Ref ID J:103114]

Adolfo Arganaraz G; Regina Perosa S; Cristina Lencioni E; Bader M; Abrao Cavalheiro E; da Graca Naffah-Mazzacoratti M; Bosco Pesquero J; Antonio Silva J Jr. 2004. Role of kinin B1 and B2 receptors in the development of pilocarpine model of epilepsy. Brain Res 1013(1):30-9. [PubMed: 15196965]  [MGI Ref ID J:90943]

Alfie ME; Alim S; Mehta D; Shesely EG; Carretero OA. 1999. An enhanced effect of arginine vasopressin in bradykinin B2 receptor null mutant mice. Hypertension 33(6):1436-40. [PubMed: 10373229]  [MGI Ref ID J:56192]

Alfie ME; Yang XP; Hess F; Carretero OA. 1996. Salt-sensitive hypertension in bradykinin B2 receptor knockout mice. Biochem Biophys Res Commun 224(3):625-30. [PubMed: 8713099]  [MGI Ref ID J:34497]

Aliberti J; Viola JP; Vieira-de-Abreu A; Bozza PT; Sher A; Scharfstein J. 2003. Cutting edge: Bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization. J Immunol 170(11):5349-53. [PubMed: 12759407]  [MGI Ref ID J:83453]

Barros CC; Haro A; Russo FJ; Schadock I; Almeida SS; Reis FC; Moraes MR; Haidar A; Hirata AE; Mori M; Bacurau RF; Wurtele M; Bader M; Pesquero JB; Araujo RC. 2012. Bradykinin inhibits hepatic gluconeogenesis in obese mice. Lab Invest 92(10):1419-27. [PubMed: 22868909]  [MGI Ref ID J:188609]

Bergaya S; Meneton P; Bloch-Faure M; Mathieu E; Alhenc-Gelas F; Levy BI; Boulanger CM. 2001. Decreased flow-dependent dilation in carotid arteries of tissue kallikrein-knockout mice. Circ Res 88(6):593-9. [PubMed: 11282893]  [MGI Ref ID J:115590]

Bernstein KE; Xiao HD; Frenzel K; Li P; Shen XZ; Adams JW; Fuchs S. 2005. Six truisms concerning ACE and the renin-angiotensin system educed from the genetic analysis of mice. Circ Res 96(11):1135-44. [PubMed: 15947253]  [MGI Ref ID J:109628]

Bhagat TD; Zhou L; Sokol L; Kessel R; Caceres G; Gundabolu K; Tamari R; Gordon S; Mantzaris I; Jodlowski T; Yu Y; Jing X; Polineni R; Bhatia K; Pellagatti A; Boultwood J; Kambhampati S; Steidl U; Stein C; Ju W; Liu G; Kenny P; List A; Bitzer M; Verma A. 2013. miR-21 mediates hematopoietic suppression in MDS by activating TGF-beta signaling. Blood 121(15):2875-81. [PubMed: 23390194]  [MGI Ref ID J:196470]

Blaes N; Pecher C; Mehrenberger M; Cellier E; Praddaude F; Chevalier J; Tack I; Couture R; Girolami JP. 2012. Bradykinin inhibits high glucose- and growth factor-induced collagen synthesis in mesangial cells through the B2-kinin receptor. Am J Physiol Renal Physiol 303(2):F293-303. [PubMed: 22573379]  [MGI Ref ID J:187019]

Borkowski JA; Ransom RW; Seabrook GR; Trumbauer M; Chen H; Hill RG; Strader CD; Hess JF. 1995. Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons. J Biol Chem 270(23):13706-10. [PubMed: 7775424]  [MGI Ref ID J:25953]

Brochu I; Labonte J; Bkaily G; D'Orleans-Juste P. 2002. Role of endothelin receptors in the hypertensive state of kinin B(2) knockout mice subjected to a high-salt diet. Clin Sci (Lond) 103 Suppl 48:380S-384S. [PubMed: 12193127]  [MGI Ref ID J:103135]

Cervenka L; Harrison-Bernard LM; Dipp S; Primrose G; Imig JD; El-Dahr SS. 1999. Early onset salt-sensitive hypertension in bradykinin B(2) receptor null mice. Hypertension 34(2):176-80. [PubMed: 10454437]  [MGI Ref ID J:88466]

Cervenka L; Vaneckova I; Maly J; Horacek V; El-Dahr SS. 2003. Genetic inactivation of the B2 receptor in mice worsens two-kidney, one-clip hypertension: role of NO and the AT2 receptor. J Hypertens 21(8):1531-8. [PubMed: 12872048]  [MGI Ref ID J:106003]

Diehl SA; McElvany B; Noubade R; Seeberger N; Harding B; Spach K; Teuscher C. 2014. G proteins Galphai1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun 82(2):773-82. [PubMed: 24478091]  [MGI Ref ID J:209809]

Duka I; Kintsurashvili E; Gavras I; Johns C; Bresnahan M; Gavras H. 2001. Vasoactive potential of the b(1) bradykinin receptor in normotension and hypertension. Circ Res 88(3):275-81. [PubMed: 11179194]  [MGI Ref ID J:115601]

Duka I; Shenouda S; Johns C; Kintsurashvili E; Gavras I; Gavras H. 2001. Role of the B(2) receptor of bradykinin in insulin sensitivity. Hypertension 38(6):1355-60. [PubMed: 11751717]  [MGI Ref ID J:103241]

Dutra RC; Bento AF; Leite DF; Manjavachi MN; Marcon R; Bicca MA; Pesquero JB; Calixto JB. 2013. The role of kinin B1 and B2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: evidence for the involvement of astrocytes. Neurobiol Dis 54:82-93. [PubMed: 23454198]  [MGI Ref ID J:197950]

Dutra RC; Leite DF; Bento AF; Manjavachi MN; Patricio ES; Figueiredo CP; Pesquero JB; Calixto JB. 2011. The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice. PLoS One 6(11):e27875. [PubMed: 22132157]  [MGI Ref ID J:201039]

El-Dahr SS; Aboudehen K; Dipp S. 2008. Bradykinin B2 receptor null mice harboring a Ser23-to-Ala substitution in the p53 gene are protected from renal dysgenesis. Am J Physiol Renal Physiol 295(5):F1404-13. [PubMed: 18753293]  [MGI Ref ID J:140998]

El-Dahr SS; Harrison-Bernard LM; Dipp S; Yosipiv IV; Meleg-Smith S. 2000. Bradykinin B2 null mice are prone to renal dysplasia: gene-environment interactions in kidney development Physiol Genomics 3(3):121-31. [PubMed: 11015607]  [MGI Ref ID J:65386]

Emanueli C; Fink E; Milia AF; Salis MB; Conti M; Demontis MP; Madeddu P. 1998. Enhanced blood pressure sensitivity to deoxycorticosterone in mice with disruption of bradykinin B2 receptor gene. Hypertension 31(6):1278-83. [PubMed: 9622142]  [MGI Ref ID J:48384]

Emanueli C; Maestri R; Corradi D; Marchione R; Minasi A; Tozzi MG; Salis MB; Straino S; Capogrossi MC; Olivetti G; Madeddu P. 1999. Dilated and failing cardiomyopathy in bradykinin B(2) receptor knockout mice [see comments] Circulation 100(23):2359-65. [PubMed: 10587341]  [MGI Ref ID J:59835]

Fan H; Harrell JR; Dipp S; Saifudeen Z; El-Dahr SS. 2005. A novel pathological role of p53 in kidney development revealed by gene-environment interactions. Am J Physiol Renal Physiol 288(1):F98-107. [PubMed: 15383401]  [MGI Ref ID J:104678]

Fan H; Stefkova J; El-Dahr SS. 2006. Susceptibility to metanephric apoptosis in bradykinin B2 receptor null mice via the p53-Bax pathway. Am J Physiol Renal Physiol 291(3):F670-82. [PubMed: 16571598]  [MGI Ref ID J:111678]

Fang C; Stavrou E; Schmaier AA; Grobe N; Morris M; Chen A; Nieman MT; Adams GN; LaRusch G; Zhou Y; Bilodeau ML; Mahdi F; Warnock M; Schmaier AH. 2013. Angiotensin 1-7 and Mas decrease thrombosis in Bdkrb2-/- mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation. Blood 121(15):3023-32. [PubMed: 23386129]  [MGI Ref ID J:196472]

Ferreira J; Campos MM; Pesquero JB; Araujo RC; Bader M; Calixto JB. 2001. Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B1 and B2 receptor knockout mice. Neuropharmacology 41(8):1006-12. [PubMed: 11747905]  [MGI Ref ID J:179423]

Han ED; MacFarlane RC; Mulligan AN; Scafidi J; Davis AE 3rd. 2002. Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Invest 109(8):1057-63. [PubMed: 11956243]  [MGI Ref ID J:76090]

Harrison-Bernard LM; Dipp S; El-Dahr SS. 2003. Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice. Am J Physiol Regul Integr Comp Physiol 285(4):R782-90. [PubMed: 12805091]  [MGI Ref ID J:84494]

Hess JF; Chen RZ; Hey P; Breese R; Chang RS; Chen TB; Bock MG; Vogt T; Pettibone DJ. 2006. Generation and characterization of a humanized bradykinin B1 receptor mouse. Biol Chem 387(2):195-201. [PubMed: 16497152]  [MGI Ref ID J:135789]

Hillmeister P; Gatzke N; Dulsner A; Bader M; Schadock I; Hoefer I; Hamann I; Infante-Duarte C; Jung G; Troidl K; Urban D; Stawowy P; Frentsch M; Li M; Nagorka S; Wang H; Shi Y; le Noble F; Buschmann I. 2011. Arteriogenesis is modulated by bradykinin receptor signaling. Circ Res 109(5):524-33. [PubMed: 21719759]  [MGI Ref ID J:186598]

Isbell DC; Voros S; Yang Z; DiMaria JM; Berr SS; French BA; Epstein FH; Bishop SP; Wang H; Roy RJ; Kemp BA; Matsubara H; Carey RM; Kramer CM. 2007. Interaction between bradykinin subtype 2 and angiotensin II type 2 receptors during post-MI left ventricular remodeling. Am J Physiol Heart Circ Physiol 293(6):H3372-8. [PubMed: 17933966]  [MGI Ref ID J:132208]

Jaffa MA; Kobeissy F; Al Hariri M; Chalhoub H; Eid A; Ziyadeh FN; Jaffa AA. 2012. Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes. PLoS One 7(9):e44714. [PubMed: 23028588]  [MGI Ref ID J:191871]

Kahn R; Hellmark T; Leeb-Lundberg LM; Akbari N; Todiras M; Olofsson T; Wieslander J; Christensson A; Westman K; Bader M; Muller-Esterl W; Karpman D. 2009. Neutrophil-derived proteinase 3 induces kallikrein-independent release of a novel vasoactive kinin. J Immunol 182(12):7906-15. [PubMed: 19494315]  [MGI Ref ID J:149285]

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]

Krankel N; Kuschnerus K; Muller M; Speer T; Mocharla P; Madeddu P; Bader M; Luscher TF; Landmesser U. 2013. Novel insights into the critical role of bradykinin and the kinin B2 receptor for vascular recruitment of circulating endothelial repair-promoting mononuclear cell subsets: alterations in patients with coronary disease. Circulation 127(5):594-603. [PubMed: 23275384]  [MGI Ref ID J:210277]

Lu F; Chauhan AK; Fernandes SM; Walsh MT; Wagner DD; Davis AE 3rd. 2008. The effect of C1 inhibitor on intestinal ischemia and reperfusion injury. Am J Physiol Gastrointest Liver Physiol 295(5):G1042-9. [PubMed: 18787060]  [MGI Ref ID J:142529]

Madeddu P; Emanueli C; Gaspa L; Salis B; Milia AF; Chao L; Chao J. 1999. Role of the bradykinin B2 receptor in the maturation of blood pressure phenotype: lesson from transgenic and knockout mice Immunopharmacology 44(1-2):9-13. [PubMed: 10604518]  [MGI Ref ID J:59794]

Madeddu P; Emanueli C; Maestri R; Salis MB; Minasi A; Capogrossi MC; Olivetti G. 2000. Angiotensin II type 1 receptor blockade prevents cardiac remodeling in bradykinin B(2) receptor knockout mice Hypertension 35(1 Pt 2):391-6. [PubMed: 10642330]  [MGI Ref ID J:60047]

Madeddu P; Salis MB; Emanueli C. 1999. Altered baroreflex control of heart rate in bradykinin B2-receptor knockout mice Immunopharmacology 45(1-3):21-7. [PubMed: 10614985]  [MGI Ref ID J:59776]

Madeddu P; Varoni MV; Palomba D; Emanueli C; Demontis MP; Glorioso N; Dessi-Fulgheri P; Sarzani R; Anania V. 1997. Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. Circulation 96(10):3570-8. [PubMed: 9396457]  [MGI Ref ID J:112265]

Maestri R; Milia AF; Salis MB; Graiani G; Lagrasta C; Monica M; Corradi D; Emanueli C; Madeddu P. 2003. Cardiac hypertrophy and microvascular deficit in kinin B2 receptor knockout mice. Hypertension 41(5):1151-5. [PubMed: 12654715]  [MGI Ref ID J:103026]

Maul B; Krause W; Pankow K; Becker M; Gembardt F; Alenina N; Walther T; Bader M; Siems WE. 2005. Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J 19(11):1474-81. [PubMed: 16126915]  [MGI Ref ID J:101196]

Milia AF; Gross V; Plehm R; De Silva JA Jr; Bader M; Luft FC. 2001. Normal blood pressure and renal function in mice lacking the bradykinin B(2) receptor. Hypertension 37(6):1473-9. [PubMed: 11408397]  [MGI Ref ID J:103234]

Monteiro AC; Schmitz V; Svensjo E; Gazzinelli RT; Almeida IC; Todorov A; de Arruda LB; Torrecilhas AC; Pesquero JB; Morrot A; Bouskela E; Bonomo A; Lima AP; Muller-Esterl W; Scharfstein J. 2006. Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi. J Immunol 177(9):6325-35. [PubMed: 17056563]  [MGI Ref ID J:140513]

Picard N; Eladari D; El Moghrabi S; Planes C; Bourgeois S; Houillier P; Wang Q; Burnier M; Deschenes G; Knepper MA; Meneton P; Chambrey R. 2008. Defective ENaC processing and function in tissue kallikrein-deficient mice. J Biol Chem 283(8):4602-11. [PubMed: 18086683]  [MGI Ref ID J:132178]

Prediger RD; Medeiros R; Pandolfo P; Duarte FS; Passos GF; Pesquero JB; Campos MM; Calixto JB; Takahashi RN. 2008. Genetic deletion or antagonism of kinin B(1) and B(2) receptors improves cognitive deficits in a mouse model of Alzheimer's disease. Neuroscience 151(3):631-43. [PubMed: 18191900]  [MGI Ref ID J:135258]

Rhaleb NE; Peng H; Alfie ME; Shesely EG; Carretero OA. 1999. Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension in mice: do kinin B2 receptors play a role? Hypertension 33(1 Pt 2):329-34. [PubMed: 9931125]  [MGI Ref ID J:53680]

Rodi D; Buzzi A; Barbieri M; Zucchini S; Verlengia G; Binaschi A; Regoli D; Boschi A; Ongali B; Couture R; Simonato M. 2013. Bradykinin B receptors increase hippocampal excitability and susceptibility to seizures in mice. Neuroscience 248C:392-402. [PubMed: 23811399]  [MGI Ref ID J:207053]

Rodrigues ES; Martin RP; Felipe SA; Bader M; Oliveira SM; Shimuta SI. 2009. Cross talk between kinin and angiotensin II receptors in mouse abdominal aorta. Biol Chem 390(9):907-13. [PubMed: 19453270]  [MGI Ref ID J:164962]

Rupniak NM; Boyce S; Webb JK; Williams AR; Carlson EJ; Hill RG ; Borkowski JA ; Hess JF. 1997. Effects of the bradykinin B1 receptor antagonist des-Arg9[Leu8]bradykinin and genetic disruption of the B2 receptor on nociception in rats and mice. Pain 71(1):89-97. [PubMed: 9200178]  [MGI Ref ID J:41328]

Sanchez de Miguel L; Neysari S; Jakob S; Petrimpol M; Butz N; Banfi A; Zaugg CE; Humar R; Battegay EJ. 2008. B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart. Cardiovasc Res 80(1):106-13. [PubMed: 18566101]  [MGI Ref ID J:161893]

Schanstra JP; Bachvarova M; Neau E; Bascands JL; Bachvarov D. 2007. Gene expression profiling in the remnant kidney model of wild type and kinin B1 and B2 receptor knockout mice. Kidney Int 72(4):442-54. [PubMed: 17579666]  [MGI Ref ID J:152886]

Schanstra JP; Duchene J; Praddaude F; Bruneval P; Tack I; Chevalier J; Girolami JP; Bascands JL. 2003. Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the bradykinin B2 receptor. Am J Physiol Heart Circ Physiol 284(6):H1904-8. [PubMed: 12560214]  [MGI Ref ID J:83895]

Schanstra JP; Neau E; Drogoz P; Arevalo Gomez MA; Lopez Novoa JM; Calise D; Pecher C; Bader M; Girolami JP; Bascands JL. 2002. In vivo bradykinin B2 receptor activation reduces renal fibrosis. J Clin Invest 110(3):371-9. [PubMed: 12163456]  [MGI Ref ID J:78354]

Shariat-Madar Z; Mahdi F; Warnock M; Homeister JW; Srikanth S; Krijanovski Y; Murphey LJ; Jaffa AA; Schmaier AH. 2006. Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin. Blood 108(1):192-9. [PubMed: 16514058]  [MGI Ref ID J:135575]

Silvestre JS; Bergaya S; Tamarat R; Duriez M; Boulanger CM; Levy BI. 2001. Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway. Circ Res 89(8):678-83. [PubMed: 11597990]  [MGI Ref ID J:115630]

Song JJ; Hwang I; Cho KH; Garcia MA; Kim AJ; Wang TH; Lindstrom TM; Lee AT; Nishimura T; Zhao L; Morser J; Nesheim M; Goodman SB; Lee DM; Bridges SL Jr; Gregersen PK; Leung LL; Robinson WH. 2011. Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis. J Clin Invest 121(9):3517-27. [PubMed: 21804193]  [MGI Ref ID J:178261]

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Trabold F; Pons S; Hagege AA; Bloch-Faure M; Alhenc-Gelas F; Giudicelli JF; Richer-Giudicelli C; Meneton P. 2002. Cardiovascular phenotypes of kinin B2 receptor- and tissue kallikrein-deficient mice. Hypertension 40(1):90-5. [PubMed: 12105144]  [MGI Ref ID J:103162]

Trevisani M; Schmidlin F; Tognetto M; Nijkamp FP; Gies JP; Frossard N; Amadesi S; Folkerts G; Geppetti P. 1999. Evidence for in vitro expression of B1 receptor in the mouse trachea and urinary bladder. Br J Pharmacol 126(6):1293-300. [PubMed: 10217521]  [MGI Ref ID J:54390]

Vashistha H; Singhal PC; Malhotra A; Husain M; Mathieson P; Saleem MA; Kuriakose C; Seshan S; Wilk A; Delvalle L; Peruzzi F; Giorgio M; Pelicci PG; Smithies O; Kim HS; Kakoki M; Reiss K; Meggs LG. 2012. Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney. Am J Physiol Renal Physiol 303(12):F1629-40. [PubMed: 23019230]  [MGI Ref ID J:190320]

Wang H; Kohno T; Amaya F; Brenner GJ; Ito N; Allchorne A; Ji RR; Woolf CJ. 2005. Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission. J Neurosci 25(35):7986-92. [PubMed: 16135755]  [MGI Ref ID J:100473]

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Ins2Akita related

Abudukadier A; Fujita Y; Obara A; Ohashi A; Fukushima T; Sato Y; Ogura M; Nakamura Y; Fujimoto S; Hosokawa M; Hasegawa H; Inagaki N. 2013. Tetrahydrobiopterin has a glucose-lowering effect by suppressing hepatic gluconeogenesis in an endothelial nitric oxide synthase-dependent manner in diabetic mice. Diabetes 62(9):3033-43. [PubMed: 23649519]  [MGI Ref ID J:208962]

Aghdam SY; Gurel Z; Ghaffarieh A; Sorenson CM; Sheibani N. 2013. High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications. Biochem Biophys Res Commun 432(2):339-44. [PubMed: 23391566]  [MGI Ref ID J:198848]

Akimov NP; Renteria RC. 2012. Spatial frequency threshold and contrast sensitivity of an optomotor behavior are impaired in the Ins2Akita mouse model of diabetes. Behav Brain Res 226(2):601-5. [PubMed: 21963766]  [MGI Ref ID J:180197]

Asakawa A; Toyoshima M; Inoue K; Koizumi A. 2007. Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system. Int J Mol Med 19(4):649-52. [PubMed: 17334640]  [MGI Ref ID J:125256]

Awad AS; Kinsey GR; Khutsishvili K; Gao T; Bolton WK; Okusa MD. 2011. Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury. Am J Physiol Renal Physiol 301(6):F1358-66. [PubMed: 21880831]  [MGI Ref ID J:180042]

Bachar-Wikstrom E; Wikstrom JD; Ariav Y; Tirosh B; Kaiser N; Cerasi E; Leibowitz G. 2013. Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes 62(4):1227-37. [PubMed: 23274896]  [MGI Ref ID J:208584]

Barber AJ; Antonetti DA; Kern TS; Reiter CE; Soans RS; Krady JK; Levison SW; Gardner TW; Bronson SK. 2005. The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalmol Vis Sci 46(6):2210-8. [PubMed: 15914643]  [MGI Ref ID J:99412]

Basu R; Lee J; Wang Z; Patel VB; Fan D; Das SK; Liu GC; John R; Scholey JW; Oudit GY; Kassiri Z. 2012. Loss of TIMP3 selectively exacerbates diabetic nephropathy. Am J Physiol Renal Physiol 303(9):F1341-52. [PubMed: 22896043]  [MGI Ref ID J:189948]

Basu R; Oudit GY; Wang X; Zhang L; Ussher JR; Lopaschuk GD; Kassiri Z. 2009. Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function. Am J Physiol Heart Circ Physiol 297(6):H2096-108. [PubMed: 19801494]  [MGI Ref ID J:158228]

Blum B; Roose AN; Barrandon O; Maehr R; Arvanites AC; Davidow LS; Davis JC; Peterson QP; Rubin LL; Melton DA. 2014. Reversal of beta cell de-differentiation by a small molecule inhibitor of the TGFbeta pathway. Elife 3:e02809. [PubMed: 25233132]  [MGI Ref ID J:218054]

Bostrom KI; Jumabay M; Matveyenko A; Nicholas SB; Yao Y. 2011. Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res 108(4):446-57. [PubMed: 21193740]  [MGI Ref ID J:183498]

Bugger H; Boudina S; Hu XX; Tuinei J; Zaha VG; Theobald HA; Yun UJ; McQueen AP; Wayment B; Litwin SE; Abel ED. 2008. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes 57(11):2924-32. [PubMed: 18678617]  [MGI Ref ID J:142159]

Bugger H; Chen D; Riehle C; Soto J; Theobald HA; Hu XX; Ganesan B; Weimer BC; Abel ED. 2009. Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 58(9):1986-97. [PubMed: 19542201]  [MGI Ref ID J:154406]

Chacko BK; Reily C; Srivastava A; Johnson MS; Ye Y; Ulasova E; Agarwal A; Zinn KR; Murphy MP; Kalyanaraman B; Darley-Usmar V. 2010. Prevention of diabetic nephropathy in Ins2(+/)(AkitaJ) mice by the mitochondria-targeted therapy MitoQ. Biochem J 432(1):9-19. [PubMed: 20825366]  [MGI Ref ID J:166866]

Chang AS; Dale AN; Moley KH. 2005. Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis. Endocrinology 146(5):2445-53. [PubMed: 15718275]  [MGI Ref ID J:129826]

Chang JH; Paik SY; Mao L; Eisner W; Flannery PJ; Wang L; Tang Y; Mattocks N; Hadjadj S; Goujon JM; Ruiz P; Gurley SB; Spurney RF. 2012. Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion. PLoS One 7(4):e33942. [PubMed: 22496773]  [MGI Ref ID J:187110]

Chavali V; Tyagi SC; Mishra PK. 2012. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun 425(3):668-72. [PubMed: 22842467]  [MGI Ref ID J:188036]

Chen H; Li J; Jiao L; Petersen RB; Li J; Peng A; Zheng L; Huang K. 2014. Apelin inhibits the development of diabetic nephropathy by regulating histone acetylation in Akita mouse. J Physiol 592(Pt 3):505-21. [PubMed: 24247978]  [MGI Ref ID J:217958]

Cheng L; Han X; Shi Y. 2009. A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice. Am J Physiol Endocrinol Metab 297(6):E1276-82. [PubMed: 19773578]  [MGI Ref ID J:159566]

Choeiri C; Hewitt K; Durkin J; Simard CJ; Renaud JM; Messier C. 2005. Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2(C96Y) Akita mice. Behav Brain Res 157(1):31-8. [PubMed: 15617768]  [MGI Ref ID J:95284]

Dennis MD; Schrufer TL; Bronson SK; Kimball SR; Jefferson LS. 2011. Hyperglycemia-Induced O-GlcNAcylation and Truncation of 4E-BP1 Protein in Liver of a Mouse Model of Type 1 Diabetes. J Biol Chem 286(39):34286-97. [PubMed: 21840999]  [MGI Ref ID J:176719]

Dokun AO; Chen L; Lanjewar SS; Lye RJ; Annex BH. 2014. Glycaemic control improves perfusion recovery and VEGFR2 protein expression in diabetic mice following experimental PAD. Cardiovasc Res 101(3):364-72. [PubMed: 24385342]  [MGI Ref ID J:220054]

Drapeau N; Lizotte F; Denhez B; Guay A; Kennedy CR; Geraldes P. 2013. Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes. Am J Physiol Endocrinol Metab 304(11):E1188-98. [PubMed: 23531619]  [MGI Ref ID J:198982]

Dugan LL; You YH; Ali SS; Diamond-Stanic M; Miyamoto S; DeCleves AE; Andreyev A; Quach T; Ly S; Shekhtman G; Nguyen W; Chepetan A; Le TP; Wang L; Xu M; Paik KP; Fogo A; Viollet B; Murphy A; Brosius F; Naviaux RK; Sharma K. 2013. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123(11):4888-99. [PubMed: 24135141]  [MGI Ref ID J:204683]

Fang RC; Kryger ZB; Buck Ii DW; De La Garza M; Galiano RD; Mustoe TA. 2010. Limitations of the db/db mouse in translational wound healing research: Is the NONcNZO10 polygenic mouse model superior? Wound Repair Regen :. [PubMed: 20955341]  [MGI Ref ID J:165705]

Faulhaber-Walter R; Chen L; Oppermann M; Kim SM; Huang Y; Hiramatsu N; Mizel D; Kajiyama H; Zerfas P; Briggs JP; Kopp JB; Schnermann J. 2008. Lack of A1 adenosine receptors augments diabetic hyperfiltration and glomerular injury. J Am Soc Nephrol 19(4):722-30. [PubMed: 18256360]  [MGI Ref ID J:149926]

Fox R; Kim HS; Reddick RL; Kujoth GC; Prolla TA; Tsutsumi S; Wada Y; Smithies O; Maeda N. 2011. Mitochondrial DNA polymerase editing mutation, PolgD257A, reduces the diabetic phenotype of Akita male mice by suppressing appetite. Proc Natl Acad Sci U S A 108(21):8779-84. [PubMed: 21555558]  [MGI Ref ID J:171899]

Fox TE; Bewley MC; Unrath KA; Pedersen MM; Anderson RE; Jung DY; Jefferson LS; Kim JK; Bronson SK; Flanagan JM; Kester M. 2011. Circulating sphingolipid biomarkers in models of type 1 diabetes. J Lipid Res 52(3):509-17. [PubMed: 21068007]  [MGI Ref ID J:170277]

Fragiadaki M; Hill N; Hewitt R; Bou-Gharios G; Cook T; Tam FW; Domin J; Mason RM. 2012. Hyperglycemia causes renal cell damage via CCN2-induced activation of the TrkA receptor: implications for diabetic nephropathy. Diabetes 61(9):2280-8. [PubMed: 22586581]  [MGI Ref ID J:208460]

Gambhir D; Ananth S; Veeranan-Karmegam R; Elangovan S; Hester S; Jennings E; Offermanns S; Nussbaum JJ; Smith SB; Thangaraju M; Ganapathy V; Martin PM. 2012. GPR109A as an anti-inflammatory receptor in retinal pigment epithelial cells and its relevance to diabetic retinopathy. Invest Ophthalmol Vis Sci 53(4):2208-17. [PubMed: 22427566]  [MGI Ref ID J:196849]

Gastinger MJ; Kunselman AR; Conboy EE; Bronson SK; Barber AJ. 2008. Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. Invest Ophthalmol Vis Sci 49(6):2635-42. [PubMed: 18515593]  [MGI Ref ID J:137045]

Gastinger MJ; Singh RS; Barber AJ. 2006. Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Invest Ophthalmol Vis Sci 47(7):3143-50. [PubMed: 16799061]  [MGI Ref ID J:112243]

Grasemann C; Devlin MJ; Rzeczkowska PA; Herrmann R; Horsthemke B; Hauffa BP; Grynpas M; Alm C; Bouxsein ML; Palmert MR. 2012. Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring. PLoS One 7(11):e50210. [PubMed: 23209676]  [MGI Ref ID J:195000]

Grutzmacher C; Park S; Zhao Y; Morrison ME; Sheibani N; Sorenson CM. 2013. Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes. Am J Physiol Renal Physiol 304(1):F19-30. [PubMed: 23077100]  [MGI Ref ID J:191244]

Guo C; Zhang Z; Zhang P; Makita J; Kawada H; Blessing K; Kador PF. 2014. Novel transgenic mouse models develop retinal changes associated with early diabetic retinopathy similar to those observed in rats with diabetes mellitus. Exp Eye Res 119:77-87. [PubMed: 24370601]  [MGI Ref ID J:210369]

Gupta S; McGrath B; Cavener DR. 2010. PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway. Diabetes 59(8):1937-47. [PubMed: 20530744]  [MGI Ref ID J:169638]

Gurel Z; Sieg KM; Shallow KD; Sorenson CM; Sheibani N. 2013. Retinal O-linked N-acetylglucosamine protein modifications: implications for postnatal retinal vascularization and the pathogenesis of diabetic retinopathy. Mol Vis 19:1047-59. [PubMed: 23734074]  [MGI Ref ID J:203213]

Gurley SB; Clare SE; Snow KP; Hu A; Meyer TW; Coffman TM. 2006. Impact of genetic background on nephropathy in diabetic mice. Am J Physiol Renal Physiol 290(1):F214-22. [PubMed: 16118394]  [MGI Ref ID J:104083]

Gurley SB; Mach CL; Stegbauer J; Yang J; Snow KP; Hu A; Meyer TW; Coffman TM. 2010. Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice. Am J Physiol Renal Physiol 298(3):F788-95. [PubMed: 20042456]  [MGI Ref ID J:157873]

Gyurko R; Siqueira CC; Caldon N; Gao L; Kantarci A; Van Dyke TE. 2006. Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. J Immunol 177(10):7250-6. [PubMed: 17082643]  [MGI Ref ID J:140617]

Ha Y; Dun Y; Thangaraju M; Duplantier J; Dong Z; Liu K; Ganapathy V; Smith SB. 2011. Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons. Invest Ophthalmol Vis Sci 52(1):527-40. [PubMed: 20811050]  [MGI Ref ID J:171562]

Han Z; Guo J; Conley SM; Naash MI. 2013. Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy. Invest Ophthalmol Vis Sci 54(1):574-84. [PubMed: 23221078]  [MGI Ref ID J:214574]

Haseyama T; Fujita T; Hirasawa F; Tsukada M; Wakui H; Komatsuda A; Ohtani H; Miura AB; Imai H; Koizumi A. 2002. Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouse. Tohoku J Exp Med 198(4):233-44. [PubMed: 12630555]  [MGI Ref ID J:107880]

Hathaway CK; Gasim AM; Grant R; Chang AS; Kim HS; Madden VJ; Bagnell CR Jr; Jennette JC; Smithies O; Kakoki M. 2015. Low TGFbeta1 expression prevents and high expression exacerbates diabetic nephropathy in mice. Proc Natl Acad Sci U S A 112(18):5815-20. [PubMed: 25902541]  [MGI Ref ID J:221419]

Hirosawa M; Minata M; Harada KH; Hitomi T; Krust A; Koizumi A. 2008. Ablation of estrogen receptor alpha (ERalpha) prevents upregulation of POMC by leptin and insulin. Biochem Biophys Res Commun 371(2):320-3. [PubMed: 18439911]  [MGI Ref ID J:136249]

Hodish I; Absood A; Liu L; Liu M; Haataja L; Larkin D; Al-Khafaji A; Zaki A; Arvan P. 2011. In vivo misfolding of proinsulin below the threshold of frank diabetes. Diabetes 60(8):2092-101. [PubMed: 21677281]  [MGI Ref ID J:186814]

Hombrebueno JR; Chen M; Penalva RG; Xu H. 2014. Loss of synaptic connectivity, particularly in second order neurons is a key feature of diabetic retinal neuropathy in the Ins2Akita mouse. PLoS One 9(5):e97970. [PubMed: 24848689]  [MGI Ref ID J:216322]

Hong EG; Jung DY; Ko HJ; Zhang Z; Ma Z; Jun JY; Kim JH; Sumner AD; Vary TC; Gardner TW; Bronson SK; Kim JK. 2007. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab 293(6):E1687-96. [PubMed: 17911348]  [MGI Ref ID J:130021]

Howard AC; McNeil AK; Xiong F; Xiong WC; McNeil PL. 2011. A novel cellular defect in diabetes: membrane repair failure. Diabetes 60(11):3034-43. [PubMed: 21940783]  [MGI Ref ID J:189473]

Howell SJ; Mekhail MN; Azem R; Ward NL; Kern TS. 2013. Degeneration of retinal ganglion cells in diabetic dogs and mice: relationship to glycemic control and retinal capillary degeneration. Mol Vis 19:1413-21. [PubMed: 23825921]  [MGI Ref ID J:200768]

Hu Y; Chen Y; Ding L; He X; Takahashi Y; Gao Y; Shen W; Cheng R; Chen Q; Qi X; Boulton ME; Ma JX. 2013. Pathogenic role of diabetes-induced PPAR-alpha down-regulation in microvascular dysfunction. Proc Natl Acad Sci U S A 110(38):15401-6. [PubMed: 24003152]  [MGI Ref ID J:201158]

Huang H; Gandhi JK; Zhong X; Wei Y; Gong J; Duh EJ; Vinores SA. 2011. TNFalpha is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis. Invest Ophthalmol Vis Sci 52(3):1336-44. [PubMed: 21212173]  [MGI Ref ID J:171543]

Iwakura H; Akamizu T; Ariyasu H; Irako T; Hosoda K; Nakao K; Kangawa K. 2007. Effects of ghrelin administration on decreased growth hormone status in obese animals. Am J Physiol Endocrinol Metab 293(3):E819-25. [PubMed: 17595213]  [MGI Ref ID J:125421]

Izumi T; Yokota-Hashimoto H; Zhao S; Wang J; Halban PA; Takeuchi T. 2003. Dominant negative pathogenesis by mutant proinsulin in the Akita diabetic mouse. Diabetes 52(2):409-16. [PubMed: 12540615]  [MGI Ref ID J:107156]

Jaholkowski P; Mierzejewski P; Zatorski P; Scinska A; Sienkiewicz-Jarosz H; Kaczmarek L; Samochowiec J; Filipkowski RK; Bienkowski P. 2011. Increased ethanol intake and preference in cyclin D2 knockout mice. Genes Brain Behav 10(5):551-6. [PubMed: 21429093]  [MGI Ref ID J:185702]

Johnson LA; Kim HS; Knudson MJ; Nipp CT; Yi X; Maeda N. 2013. Diabetic atherosclerosis in APOE*4 mice: synergy between lipoprotein metabolism and vascular inflammation. J Lipid Res 54(2):386-96. [PubMed: 23204275]  [MGI Ref ID J:193106]

Jun JY; Ma Z; Segar L. 2011. Spontaneously diabetic Ins2(+/Akita):apoE-deficient mice exhibit exaggerated hypercholesterolemia and atherosclerosis. Am J Physiol Endocrinol Metab 301(1):E145-54. [PubMed: 21447785]  [MGI Ref ID J:182074]

Kador PF; Zhang P; Makita J; Zhang Z; Guo C; Randazzo J; Kawada H; Haider N; Blessing K. 2012. Novel diabetic mouse models as tools for investigating diabetic retinopathy. PLoS One 7(12):e49422. [PubMed: 23251343]  [MGI Ref ID J:195671]

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]

Kayo T; Koizumi A. 1998. Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period. J Clin Invest 101(10):2112-8. [PubMed: 9593767]  [MGI Ref ID J:47883]

Kern TS; Tang J; Berkowitz BA. 2010. Validation of structural and functional lesions of diabetic retinopathy in mice. Mol Vis 16:2121-31. [PubMed: 21139688]  [MGI Ref ID J:168105]

Kezic JM; Chen X; Rakoczy EP; McMenamin PG. 2013. The effects of age and Cx3cr1 deficiency on retinal microglia in the Ins2(Akita) diabetic mouse. Invest Ophthalmol Vis Sci 54(1):854-63. [PubMed: 23307960]  [MGI Ref ID J:214564]

Kikawa K; Sakano D; Shiraki N; Tsuyama T; Kume K; Endo F; Kume S. 2014. Beneficial effect of insulin treatment on islet transplantation outcomes in Akita mice. PLoS One 9(4):e95451. [PubMed: 24743240]  [MGI Ref ID J:215198]

Kim ST; Moley KH. 2008. Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. Reproduction 136(3):313-22. [PubMed: 18558660]  [MGI Ref ID J:145654]

Kobayashi H; Yamazaki S; Takashima S; Liu W; Okuda H; Yan J; Fujii Y; Hitomi T; Harada KH; Habu T; Koizumi A. 2013. Ablation of Rnf213 retards progression of diabetes in the Akita mouse. Biochem Biophys Res Commun 432(3):519-25. [PubMed: 23410753]  [MGI Ref ID J:200802]

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Zuber C; Fan JY; Guhl B; Roth J. 2004. Misfolded proinsulin accumulates in expanded pre-Golgi intermediates and endoplasmic reticulum subdomains in pancreatic beta cells of Akita mice. FASEB J 18(7):917-9. [PubMed: 15033933]  [MGI Ref ID J:118471]

de Preux Charles AS; Verdier V; Zenker J; Peter B; Medard JJ; Kuntzer T; Beckmann JS; Bergmann S; Chrast R. 2010. Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice. PLoS One 5(5):e10832. [PubMed: 20520806]  [MGI Ref ID J:160899]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Pricing for USA, Canada and Mexico shipping destinations View International Pricing


Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2625.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing


Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3412.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

General Supply Notes

Control Information

   000664 C57BL/6J
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

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.

See Terms of Use tab for General Terms and Conditions

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.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For 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.

Contact information

General inquiries regarding Terms of Use

Contracts Administration


JAX® Mice, Products & Services Conditions of Use

"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty


In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

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 and PRODUCTS 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.