JAX Mouse Strain Datasheet - 006580

B6.Cg-Ins2^Akita Ldlr^tm1Her/J

Stock No:: 006580 |; Akita LDLR KO

Cryo Recovery

Overview

Also Known As: Akita LDLR KO

These double mutant mice carry the Akita mutation, characterized by early-onset NIDDM, and an Ldlr knock-out, characterized by increased plasma cholesterol levels.

Donating Investigator

Dr. Jan L. Breslow, Rockefeller University

Genetic overview

Genetic Background	Generation

Ins2^Akita

Allele Type	Gene Symbol	Gene Name
Spontaneous	Ins2	insulin II

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ldlr	low density lipoprotein receptor

Research Applications

Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research
Research Tools
Cell Biology Research
Endocrine Deficiency Research

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Base Price

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$2,595.00 Domestic price Cryo Recovery

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Details

Detailed 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 Ldlr^tm1Her 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 Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Ins2^Akita

Allele Symbol: Ins2^Akita

Allele Name	Akita
Allele Type	Spontaneous
Allele Synonym(s)	Akita; Akita^Ins2; Ins2^C96Y; Ins2^Mody; Mody; Mody4
Gene Symbol and Name	Ins2, insulin II
Gene Synonym(s)	AA986540; CP-II; IDDM; IDDM1; IDDM2; ILPR; IRDN; Ins-2; Ins-2; InsII; MODY10; Mody; Mody; Mody4; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4
Strain of Origin	C57BL/6NSlc
Chromosome	7
Molecular Note	In the mutant allele a transition from G to A at nucleotide 1907 disrupted an Fnu4HI site in exon 3. This mutation changed the seventh amino acid in the A chain of mature insulin, Cys96 (TGC), to Tyr (TAC). The authors predict that the transition would disrupt a disulfide bond between the A and the B chains and would likely induce a major conformational change in insulin 2 molecules. RT-PCR studies suggest that both normal and mutant Ins2 alleles are transcribed similarly in pancreatic islets of heterozygous mice, although immunofluorescence and immunoblot analyses of heterozygous islets detected reduced levels of insulin and proinsulin.

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Allele Name	targeted mutation 1, Joachim Herz
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	LDLR KO; LDLR-; LDLr-KO; LDLr0; LDLrKO; Ldlrtm1Her
Gene Symbol and Name	Ldlr, low density lipoprotein receptor
Gene Synonym(s)	FH; FHC; LDLCQ2; LDLRA
Site of Expression	Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
Strain of Origin	129S7/SvEvBrd-Hprt<+>
Chromosome	9
General Note	When used in bone marrow transplant into Ldlr^tm1Her homozygous mice, Abca1^tm1Jdm Abcg1^tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777) Phenotypic Similarity to Human Syndrome: Atherosclerosis, Susceptibility to J:29950, J:225091 in mice fed a high-cholesterol diet.
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.
Mutations Made By	Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Ins2^Akita 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

Genotype: Ldlr^tm1Her related

Cardiovascular Research
- Atherosclerosis
- Hypercholesterolemia
Metabolism Research
- Lipid Metabolism

Mammalian Phenotype Terms by Genotype

Genotype: Ins2^Akita/Ins2^Akita Ldlr^tm1Her/Ldlr^tm1Her
B6.Cg-Ins2^Akita Ldlr^tm1Her

mortality/aging

premature death
- compared with Ldlr^tm1Her homozygotes

homeostasis/metabolism phenotype

decreased circulating insulin level
- in fasting mice compared with Ldlr^tm1Her homozygotes

hyperglycemia
- severe compared with Ldlr^tm1Her homozygotes

impaired glucose tolerance
- compared with Ldlr^tm1Her homozygotes

increased circulating HDL cholesterol level
- in female mice compared with Ldlr^tm1Her homozygotes

increased circulating LDL cholesterol level
- 2-fold in male mice and 24% in female mice compared with Ldlr^tm1Her homozygotes

increased circulating VLDL cholesterol level
- 7-fold in male mice and 1.8-fold in female mice compared with Ldlr^tm1Her homozygotes

increased circulating cholesterol level
- in fasting mice compared with Ldlr^tm1Her homozygotes

increased circulating triglyceride level
- in fasting mice compared with Ldlr^tm1Her homozygotes

growth/size/body region phenotype

decreased body weight
- in male, but not female, mice at 20 weeks of age compared with Ldlr^tm1Her homozygotes

cardiovascular system phenotype

increased susceptibility to atherosclerosis
- accelerated in mice fed a high-fat diet compared with similarly treated Ldlr^tm1Her homozygotes

References

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: 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: J:40063

Additional - Ins2^Akita related

Abdo S; Shi Y; Otoukesh A; Ghosh A; Lo CS; Chenier I; Filep JG; Ingelfinger JR; Zhang SL; Chan JS. 2014. Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice. Diabetes 63(10):3483-96. PubMed: 24812425 MGI: J:229839
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: J:217958
Chen Q; Takahashi Y; Oka K; Ma JX. 2016. Functional Differences of Very-Low-Density Lipoprotein Receptor Splice Variants in Regulating Wnt Signaling. Mol Cell Biol 36(20):2645-54. PubMed: 27528615 MGI: J:236304
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: 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: J:95284
Denhez B; Lizotte F; Guimond MO; Jones N; Takano T; Geraldes P. 2015. Increased SHP-1 protein expression by high glucose levels reduces nephrin phosphorylation in podocytes. J Biol Chem 290(1):350-8. PubMed: 25404734 MGI: J:218390
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: 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: 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: 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: J:204683
Fang F; Bae EH; Hu A; Liu GC; Zhou X; Williams V; Maksimowski N; Lu C; Konvalinka A; John R; Scholey JW. 2015. Deletion of the gene for adiponectin accelerates diabetic nephropathy in the Ins2 (+/C96Y) mouse. Diabetologia 58(7):1668-78. PubMed: 25957229 MGI: J:224619
Fang RC; Kryger ZB; Buck DW 2nd; 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 18(6):605-13. PubMed: 20955341 MGI: 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: J:149926
Fort PE; Losiewicz MK; Pennathur S; Jefferson LS; Kimball SR; Abcouwer SF; Gardner TW. 2014. mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes. Diabetes 63(9):3077-90. PubMed: 24740573 MGI: J:229867
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: 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: 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: 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: J:196849
Gao J; Wang Y; Zhao X; Chen P; Xie L. 2015. MicroRNA-204-5p-Mediated Regulation of SIRT1 Contributes to the Delay of Epithelial Cell Cycle Traversal in Diabetic Corneas. Invest Ophthalmol Vis Sci 56(3):1493-504. PubMed: 25613939 MGI: J:230981
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: 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: 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: 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: 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: J:210369
Gupta I; Cahoon J; Zhang X; Jones AD; Ahmed F; Uehara H; Messenger W; Ambati BK. 2015. In vivo ZW800-microbead imaging of retinal and choroidal vascular leakage in mice. Exp Eye Res 134:155-8. PubMed: 25536533 MGI: J:230273
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: 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: 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: 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: 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: J:140617
Ha JH; Sei Y; Basile AS. 1995. Striatal met-enkephalin and substance P levels are decreased in mice infected with the LP-BM5 murine leukemia virus. J Neurochem 64(4):1896-8. PubMed: 7534338 MGI: J:23782
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: 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: 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: 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: J:221419
Hien TT; Turczynska KM; Dahan D; Ekman M; Grossi M; Sjogren J; Nilsson J; Braun T; Boettger T; Garcia-Vaz E; Stenkula K; Sward K; Gomez MF; Albinsson S. 2016. Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization. J Biol Chem 291(7):3552-68. PubMed: 26683376 MGI: J:231038
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: 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: 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: 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: 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: 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: 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: 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: J:171543
Huang H; He J; Johnson D; Wei Y; Liu Y; Wang S; Lutty GA; Duh EJ; Semba RD. 2015. Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1alpha-VEGF pathway inhibition. Diabetes 64(1):200-12. PubMed: 25187372 MGI: J:230203
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: 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: 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: 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: 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: 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: J:195671
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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: 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: J:76337
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Also Known As: Akita LDLR KO

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Genetic overview

Research Applications

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Detailed Description

Development

Control Suggestions

Additional Information

Ins2Akita

Allele Symbol: Ins2Akita

Ldlrtm1Her

Allele Symbol: Ldlrtm1Her

Disease Terms

Research Areas By Genotype

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

Genotype: Ins2Akita related

Genotype: Ldlrtm1Her related

Mammalian Phenotype Terms by Genotype

Genotype: Ins2Akita/Ins2Akita Ldlrtm1Her/Ldlrtm1HerB6.Cg-Ins2Akita Ldlrtm1Her

mortality/aging

homeostasis/metabolism phenotype

growth/size/body region phenotype

cardiovascular system phenotype

References

Additional References

Additional - Ins2Akita related

Additional - Ldlrtm1Her related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

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Ins2^Akita

Allele Symbol: Ins2^Akita

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Genotype: Ins2^Akita related

Genotype: Ldlr^tm1Her related

Genotype: Ins2^Akita/Ins2^Akita Ldlr^tm1Her/Ldlr^tm1Her
B6.Cg-Ins2^Akita Ldlr^tm1Her

Additional - Ins2^Akita related

Additional - Ldlr^tm1Her related