Strain Name:

B6.Cg-Ins2Akita Ldlrtm1Her/J

Stock Number:

006580

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Availability:

Cryopreserved - Ready for recovery

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Description

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; Mutant Strain; Spontaneous Mutation; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation?+F4p
Generation Definitions
 
Donating InvestigatorDr. Jan L. Breslow,   Rockefeller University

Description
Mice homozygous for the Akita spontaneous mutation die postnatally, typically by 12 weeks of age. Independently, heterozygous Akita mutant mice are a model of insulin dependent diabetes mellitus (IDDM) with severe hyperglycemia (see the datasheet for Stock No. 003548 for additional information). LDLR-null homozygotes have elevated serum cholesterol levels (200-400 mg/dl) which can escalate to very high levels (> 2000 mg/dl) when the mice are fed a high fat diet. LDLR-deficient mice also are predisposed to develop atherosclerosis. These double mutant mice may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, hypercholesterolemia, and diabetes-related macrovascular complications.

Development
The Ldlrtm1Her mutation was made by Dr. Robert Hammer and Joachim Herz (HHMI, University of Texas Southwestern Medical Center). Briefly, a targeting vector was used to insert a neo cassette into exon 4. The vector was electroporated into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6J, and the strain was made congenic on a C57BL/6J genetic background at The Jackson Laboratory (Stock No. 002207). The Akita spontaneous mutation in the insulin II gene (originally called Mody4) was identified on the C57BL/6NScl genetic background by Dr. Akio Koizumi (The Akita University School of Medicine). These mice were shipped to The Jackson Laboratory and then backcrossed on to the C57BL/6J genetic background (Stock No. 003548). To generate the double mutant strain, Stock No. 002207 mice were bred with Stock No. 003548 mice in the laboratory of Dr. Jan Breslow at The Rockefeller University. Double mutant mice were then backcrossed to C57BL/6J for approximately 7 generations prior to arrival at The Jackson Laboratory. The donating investigators indicate that 103/104 microsatellite markers indicate C57BL/6J background. The single exception is D7Mit81.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ins2Akita     (11 strains)

View Strains carrying   Ldlrtm1Her     (15 strains)

View Strains carrying other alleles of Ins2     (7 strains)

View Strains carrying other alleles of Ldlr     (4 strains)

Phenotype

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)
Hypercholesterolemia, Familial   (LDLR)
Insulin; INS   (INS)
Maturity-Onset Diabetes of the Young, Type 10; MODY10   (INS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ins2Akita/Ins2Akita Ldlrtm1Her/Ldlrtm1Her

        B6.Cg-Ins2Akita Ldlrtm1Her
  • mortality/aging
  • premature death
    • compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • homeostasis/metabolism phenotype
  • decreased circulating insulin level
    • in fasting mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • hyperglycemia
    • severe compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • impaired glucose tolerance
    • compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • increased circulating cholesterol level
    • in fasting mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
    • increased circulating HDL cholesterol level
      • in female mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
    • increased circulating LDL cholesterol level
      • 2-fold in male mice and 24% in female mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
    • increased circulating VLDL cholesterol level
      • 7-fold in male mice and 1.8-fold in female mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • increased circulating triglyceride level
    • in fasting mice compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • growth/size/body phenotype
  • decreased body weight
    • in male, but not female, mice at 20 weeks of age compared with Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
  • cardiovascular system phenotype
  • increased susceptibility to atherosclerosis
    • accelerated in mice fed a high-fat diet compared with similarly treated Ldlrtm1Her homozygotes   (MGI Ref ID J:174983)
View Research Applications

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

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia
Other
      altered fat metabolism

Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Type 1 Diabetes (IDDM)

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research

Ins2Akita related

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

Ldlrtm1Her related

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia

Metabolism Research
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

 
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]
 
Allele Symbol Ldlrtm1Her
Allele Name targeted mutation 1, Joachim Herz
Allele Type Targeted (Null/Knockout)
Common Name(s) LDLR KO; LDLR-; LDLr-KO; LDLr0; LDLrKO; Ldlrtm1Her;
Mutation Made ByDr. Joachim Herz,   Univ of Texas Southwest Med Ctr Dallas
Strain of Origin129S7/SvEvBrd-Hprt<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt<+>
Site of ExpressionImmunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
Gene Symbol and Name Ldlr, low density lipoprotein receptor
Chromosome 9
Gene Common Name(s) FH; FHC; LDLCQ2; LDLRA;
General Note When used in bone marrow transplant into Ldlrtm1Her homozygous mice, Abca1tm1Jdm Abcg1tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777)
Phenotypic Similarity to Human Syndrome: Type 1 Diabetic Macrovascular Disease (J:174983)
Molecular Note Insertion of a neomycin resistance cassette into exon 4. The authors predict that the targeted allele would encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals. [MGI Ref ID J:37394]

Genotyping

Genotyping Information

Genotyping Protocols

Ldlrtm1Her-alternate 1, High Resolution Melting
Ins2Akita, End Point Analysis
Ins2Akita, Pyrosequencing
Ins2Akita, Restriction Enzyme Digest


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Ishibashi S; Brown MS; Goldstein JL; Gerard RD; Hammer RE; Herz J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see comments] J Clin Invest 92(2):883-93. [PubMed: 8349823]  [MGI Ref ID J:37394]

Yoshioka M; Kayo T; Ikeda T; Koizumi A. 1997. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46(5):887-94. [PubMed: 9133560]  [MGI Ref ID J:40063]

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]

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]

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]

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]

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]

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; 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; 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]

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]

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]

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de Claro RA; Zhu X; Tang J; Morgan-Stevenson V; Schwartz BR; Iwata A; Liles WC; Raines EW; Harlan JM. 2011. Hematopoietic Fas Deficiency Does Not Affect Experimental Atherosclerotic Lesion Formation despite Inducing a Proatherogenic State. Am J Pathol 178(6):2931-7. [PubMed: 21550016]  [MGI Ref ID J:173162]

de Haan W; Out R; Berbee JF; van der Hoogt CC; van Dijk KW; van Berkel TJ; Romijn JA; Jukema JW; Havekes LM; Rensen PC. 2008. Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo. Biochem Biophys Res Commun 377(4):1294-8. [PubMed: 18992221]  [MGI Ref ID J:143183]

de Nooijer R; Bot I; von der Thusen JH; Leeuwenburgh MA; Overkleeft HS; Kraaijeveld AO; Dorland R; van Santbrink PJ; van Heiningen SH; Westra MM; Kovanen PT; Jukema JW; van der Wall EE; van Berkel TJ; Shi GP; Biessen EA. 2009. Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis. Arterioscler Thromb Vasc Biol 29(2):188-94. [PubMed: 19095996]  [MGI Ref ID J:163799]

de Oliveira J; Hort MA; Moreira EL; Glaser V; Ribeiro-do-Valle RM; Prediger RD; Farina M; Latini A; de Bem AF. 2011. Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress. Neuroscience 197:99-106. [PubMed: 21945034]  [MGI Ref ID J:184047]

de Souza JC; de Oliveira CA; Carneiro EM; Boschero AC; de Oliveira HC. 2010. Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice. Diabetologia 53(11):2461-2; author reply 2463-4. [PubMed: 20694455]  [MGI Ref ID J:166652]

van Dijk KW; van Vlijmen BJ; de Winther MP; van 't Hof B; van der Zee A; van der Boom H; Havekes LM; Hofker MH. 1999. Hyperlipidemia of ApoE2(Arg(158)-Cys) and ApoE3-Leiden transgenic mice is modulated predominantly by LDL receptor expression. Arterioscler Thromb Vasc Biol 19(12):2945-51. [PubMed: 10591674]  [MGI Ref ID J:59826]

van Eck M; Bos IS; Kaminski WE; Orso E; Rothe G; Twisk J; Bottcher A; Van Amersfoort ES; Christiansen-Weber TA; Fung-Leung WP; Van Berkel TJ; Schmitz G. 2002. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci U S A 99(9):6298-303. [PubMed: 11972062]  [MGI Ref ID J:76337]

van Es T; van Puijvelde GH; Ramos OH; Segers FM; Joosten LA; van den Berg WB; Michon IM; de Vos P; van Berkel TJ; Kuiper J. 2009. Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochem Biophys Res Commun 388(2):261-5. [PubMed: 19660432]  [MGI Ref ID J:152718]

van Gils JM; Derby MC; Fernandes LR; Ramkhelawon B; Ray TD; Rayner KJ; Parathath S; Distel E; Feig JL; Alvarez-Leite JI; Rayner AJ; McDonald TO; O'Brien KD; Stuart LM; Fisher EA; Lacy-Hulbert A; Moore KJ. 2012. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol 13(2):136-43. [PubMed: 22231519]  [MGI Ref ID J:181210]

van Leeuwen M; Kemna MJ; de Winther MP; Boon L; Duijvestijn AM; Henatsch D; Bos NA; Gijbels MJ; Tervaert JW. 2013. Passive immunization with hypochlorite-oxLDL specific antibodies reduces plaque volume in LDL receptor-deficient mice. PLoS One 8(7):e68039. [PubMed: 23874490]  [MGI Ref ID J:204410]

van Puijvelde GH; Hauer AD; de Vos P; van den Heuvel R; van Herwijnen MJ; van der Zee R; van Eden W; van Berkel TJ; Kuiper J. 2006. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation 114(18):1968-76. [PubMed: 17060383]  [MGI Ref ID J:127201]

van Vlijmen BJ; Rohlmann A; Page ST; Bensadoun A; Bos IS; van Berkel TJ; Havekes LM; Herz J. 1999. An extrahepatic receptor-associated protein-sensitive mechanism is involved in the metabolism of triglyceride-rich lipoproteins. J Biol Chem 274(49):35219-26. [PubMed: 10575007]  [MGI Ref ID J:58704]

van Vlijmen BJ; van Dijk KW; van't Hof HB; van Gorp PJ; van der Zee A; van der Boom H; Breuer ML; Hofker MH; Havekes LM. 1996. In the absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-158 --> Cys) transgenic mice develop more severe hyperlipoproteinemia than apolipoprotein E*3-Leiden transgenic mice. J Biol Chem 271(48):30595-602. [PubMed: 8940032]  [MGI Ref ID J:37473]

van der Hoogt CC; Berbee JF; Espirito Santo SM; Gerritsen G; Krom YD; van der Zee A; Havekes LM; van Dijk KW; Rensen PC. 2006. Apolipoprotein CI causes hypertriglyceridemia independent of the very-low-density lipoprotein receptor and apolipoprotein CIII in mice. Biochim Biophys Acta 1761(2):213-20. [PubMed: 16478678]  [MGI Ref ID J:110564]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as heterozygous for the Akita mutation and homozygous for the LDLR mutation.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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.

Control Information

  Control
   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


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

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

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 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.


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