Summary | Mutation origin | Mutation description | Expression | Phenotypes | Disease models | Tumor data | Find Mice (IMSR) | References

Symbol: Ins2Akita Name: insulin II; Akita MGI ID: MGI:1857572 Synonyms: Akita, AkitaIns2, Ins2C96Y, Ins2Mody, Mody, Mody4 Gene: Ins2  Location: Chr7:142232393-142233463 bp, - strand  Genetic Position: Chr7, 88.0 cM Alliance: Ins2Akita page

Abnormal glucose and insulin homeostasis in Ins2Akita/Ins2Akita and Ins2Akita/Ins2Akita Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 but not Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice. Show the 1 phenotype image(s) involving this allele.

Strain of Origin:

C57BL/6NSlc

Allele Type:    Spontaneous Mutation:    Single point mutation   Mutation details: In the mutant allele a transition from G-to-A at coding nucleotide 287 disrupts 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) (p.C96Y). 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. (J:51935) Inheritance:    Dominant

Key:	hm homozygous ht heterozygous tg involves transgenes √ phenotype observed cn conditional genotype  cx complex: > 1 genome feature ot other: hemizygous, indeterminate,... N normal phenotype
Genotype/ Background:	Allelic Composition Genetic Background Cell Line(s) Allelic Composition Genetic Background Cell Line(s) Loading... hm1  Disease Model Ins2Akita/Ins2Akita C57BL/6-Ins2Akita   hm2 Ins2Akita/Ins2Akita C57BL/6-Ins2Akita/J   hm3  Disease Model Ins2Akita/Ins2Akita C.B6N-Ins2Akita   hm4 Ins2Akita/Ins2Akita involves: C57BL/6NSlc   ht5  Disease Model Ins2Akita/Ins2+ C57BL/6-Ins2Akita   ht6  Disease Model Ins2Akita/Ins2+ C57BL/6-Ins2Akita/J   ht7 Ins2Akita/Ins2+ C.B6N-Ins2Akita   ht8 Ins2Akita/Ins2+ involves: C3H * C57BL/6NJcl * C57BL/6NSlc   ht9 Ins2Akita/Ins2+ involves: C57BL/6NSlc   cn10 Cebpbtm1.1Maka/Cebpbtm1.1Maka Ins2Akita/Ins2Akita Tg(Ins2-cre)23Herr/0 involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NSlc * CBA/J   cn11 Ins2Akita/Ins2Akita Jazf1tm1c(EUCOMM)Wtsi/Jazf1tm1c(EUCOMM)Wtsi Tg(Ins2-cre)23Herr/0 involves: 129S4/SvJaeSor * C57BL/6N * C57BL/6NSlc * CBA/J   cx12 Bdkrb2tm1Jfh/Bdkrb2tm1Jfh Ins2Akita/Ins2+ B6.Cg-Ins2Akita Bdkrb2tm1Jfh   cx13  Disease Model Ins2Akita/Ins2Akita Ldlrtm1Her/Ldlrtm1Her B6.Cg-Ins2Akita Ldlrtm1Her   cx14 Ins2Akita/Ins2+ Or12d17em1Cya/Or12d17em1Cya C57BL/6-Ins2Akita Or12d17em1Cya   cx15  Disease Model Ins2Akita/Ins2Akita Itga1tm1Gdnr/Itga1tm1Gdnr C.Cg-Ins2Akita Itga1tm1Gdnr   cx16 Ins2Akita/Ins2Akita Rpl13atm1.1Jesc/Rpl13atm1.1Jesc FVB.Cg-Rpl13atm1.1Jesc Ins2Akita   cx17 Ero1bGt(P077G11)Wrst/Ero1b+ Ins2Akita/Ins2+ involves: 129S2/SvPas * C57BL/6NSlc   cx18 Gasttm1(INS)Ez/Gast+ Ins2Akita/Ins2+ involves: 129S4/SvJae * C57BL/6NSlc   cx19 Dbm1A/J/Dbm1A/J Ins2Akita/Ins2+ involves: A/J * C57BL/6J * C57BL/6NSlc   cx20 Dbm4C57BL/6J/? Ins2Akita/Ins2+ involves: A/J * C57BL/6J * C57BL/6NSlc   cx21 Dbm3C57BL/6J/? Ins2Akita/Ins2+ involves: A/J * C57BL/6J * C57BL/6NSlc   cx22 Ins2Akita/Ins2+ Rnf213tm1.1Akoi/Rnf213tm1.1Akoi involves: C57BL/6N * C57BL/6NSlc   cx23 Ins2Akita/Ins2+ Prf1tm1Sdz/Prf1tm1Sdz Rag1tm1Mom/Rag1tm1Mom NOD.Cg-Rag1tm1Mom Ins2Akita Prf1tm1Sdz   cx24 Ins2Akita/Ins2Akita Prf1tm1Sdz/Prf1tm1Sdz Rag1tm1Mom/Rag1tm1Mom NOD.Cg-Rag1tm1Mom Ins2Akita Prf1tm1Sdz   ot25  Disease Model Ins2Akita/? involves: C57BL/6NSlc
Phenotypes:	Affected Systems hm1 hm2 hm3 hm4 ht5 ht6 ht7 ht8 ht9 cn10 cn11 cx12 cx13 cx14 cx15 cx16 cx17 cx18 cx19 cx20 cx21 cx22 cx23 cx24 ot25 show or hide all annotated terms Sex:                                               adipose tissue √ √ √ √ √ decreased subcutaneous adipose tissue amount √ √ √ √ decreased body fat mass √ decreased adipocyte glucose uptake √ increased adipocyte glucose uptake √ behavior/neurological √ √ √ √ √ increased fluid intake √ polydipsia √ √ increased food intake √ √ √ polyphagia √ increased anxiety-related response √ akinesia √ decreased locomotor activity √ √ cardiovascular system √ √ √ √ √ √ increased susceptibility to atherosclerosis √ abnormal glomerular capillary morphology √ √ abnormal retina vasculature morphology √ abnormal heart morphology √ thick interventricular septum √ abnormal heart left ventricle morphology √ heart left ventricle hypertrophy √ hematoma √ abnormal cardiac muscle contractility √ increased vascular permeability √ cellular √ √ √ √ √ √ √ √ √ decreased adipocyte glucose uptake √ increased adipocyte glucose uptake √ abnormal spermatogonia morphology √ abnormal mitochondrial morphology √ √ abnormal mitochondrial chromosome morphology √ √ abnormal pancreatic islet cell apoptosis √ increased pancreatic islet cell apoptosis √ increased pancreatic beta cell apoptosis √ increased retina apoptosis √ decreased pancreatic beta cell proliferation √ decreased skeletal muscle cell glucose uptake √ digestive/alimentary system √ √ abnormal intestinal epithelium morphology √ √ endocrine/exocrine glands √ √ √ √ √ √ √ √ √ √ √ √ √ endocrine/exocrine gland phenotype N abnormal pancreatic islet morphology √ √ √ √ √ abnormal pancreatic alpha cell morphology √ abnormal pancreatic beta cell morphology √ √ √ abnormal pancreatic beta cell mass √ decreased pancreatic beta cell mass √ √ decreased pancreatic beta cell number √ √ degranulated pancreatic beta cells √ √ small pancreatic islets √ √ abnormal seminiferous tubule morphology √ abnormal Leydig cell morphology √ √ abnormal pancreas physiology √ abnormal pancreatic islet cell apoptosis √ increased pancreatic islet cell apoptosis √ increased pancreatic beta cell apoptosis √ decreased pancreatic beta cell proliferation √ decreased insulin secretion √ √ √ √ √ √ √ √ growth/size/body √ √ √ √ √ N √ N √ √ √ √ growth/size/body region phenotype N N decreased body fat mass √ heart left ventricle hypertrophy √ decreased body weight √ √ √ √ √ √ √ √ increased body weight √ postnatal growth retardation √ √ hematopoietic system √ √ increased erythrocyte cell number √ absent mature B cells √ absent T cells √ increased leukocyte cell number √ increased granulocyte number √ increased macrophage cell number √ increased monocyte cell number √ abnormal microglial cell morphology √ homeostasis/metabolism √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ homeostasis/metabolism phenotype N N N N decreased circulating leptin level √ √ increased circulating cholesterol level √ increased circulating HDL cholesterol level √ increased circulating LDL cholesterol level √ increased circulating VLDL cholesterol level √ decreased circulating triglyceride level √ increased circulating triglyceride level √ increased energy expenditure √ √ increased carbon dioxide production √ increased oxygen consumption √ decreased respiratory quotient √ √ abnormal glucose homeostasis √ √ √ decreased insulin secretion √ √ √ √ √ √ √ √ abnormal circulating glucose level √ √ √ √ increased circulating glucose level √ √ √ √ √ √ hyperglycemia √ √ √ √ √ √ √ √ √ √ √ √ decreased circulating insulin level √ √ √ √ √ √ √ √ increased circulating insulin level √ impaired glucose tolerance √ √ √ √ √ √ √ √ increased insulin sensitivity √ insulin resistance √ decreased liver triglyceride level √ decreased skeletal muscle triglyceride level √ albuminuria √ √ √ immune system √ √ absent mature B cells √ absent T cells √ increased leukocyte cell number √ increased granulocyte number √ increased macrophage cell number √ increased monocyte cell number √ abnormal microglial cell morphology √ abnormal response to transplant √ integument √ √ √ √ decreased subcutaneous adipose tissue amount √ √ √ √ alopecia √ √ liver/biliary system √ decreased liver triglyceride level √ mortality/aging √ √ √ √ √ √ √ √ √ N √ mortality/aging N premature death √ √ √ √ √ √ √ √ postnatal lethality √ postnatal lethality, complete penetrance √ muscle √ heart left ventricle hypertrophy √ abnormal cardiac muscle contractility √ decreased skeletal muscle cell glucose uptake √ decreased skeletal muscle triglyceride level √ nervous system √ abnormal microglial cell morphology √ abnormal astrocyte morphology √ renal/urinary system √ √ √ √ √ abnormal glomerular capillary morphology √ √ albuminuria √ √ √ increased renal glomerulus basement membrane thickness √ √ abnormal glomerular mesangium morphology √ expanded mesangial matrix √ √ √ mesangiolysis √ glomerulosclerosis √ √ √ renal glomerular protein deposits √ √ abnormal kidney interstitium morphology √ √ hydronephrosis √ √ increased renal glomerular filtration rate √ √ √ polyuria √ √ reproductive system √ √ abnormal spermatogonia morphology √ abnormal seminiferous tubule morphology √ abnormal Leydig cell morphology √ √ abnormal spermatic cord morphology √ skeleton √ √ √ √ kyphosis √ √ √ √ decreased bone mineral density √ √ √ √ vision/eye √ abnormal retina vasculature morphology √ increased retina apoptosis √ abnormal retina neuronal layer morphology √ abnormal retina ganglion layer morphology √

View phenotypes and curated references for all genotypes (concatenated display).

Key:

√ disease model   expected model not found

Models:

Human Diseases hm1 hm3 ht5 ht6 cx13 cx15 ot25 diabetic angiopathy IDs diabetic angiopathy       DOID:11713 MESH:D003925 NCI:C35610 UMLS_CUI:C0011871 UMLS_CUI:C0011875 Close √ maturity-onset diabetes of the young IDs maturity-onset diabetes of the young       DOID:0050524 ICD10CM:E11.8 KEGG:04950 OMIM:606391 ORDO:552 Close √ √ permanent neonatal diabetes mellitus IDs permanent neonatal diabetes mellitus       DOID:0060639 OMIM:606176 Close √ type 1 diabetes mellitus IDs type 1 diabetes mellitus       DOID:9744 ICD10CM:E10 KEGG:04940 MESH:D003922 NCI:C2986 OMIM:222100 UMLS_CUI:C0011854 Close √ √ type 2 diabetes mellitus IDs type 2 diabetes mellitus       DOID:9352 ICD10CM:E11 KEGG:04930 MESH:D003924 NCI:C26747 OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036 UMLS_CUI:C0011860 Close √

In Mice Carrying this Mutation:	4 RNA-Seq or microarray experiment(s)
In Structures Affected by this Mutation:	28 anatomical structure(s)

List all tumor models in MMHCdb carrying Ins2Akita

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
Carrying this Mutation:	Mouse Strains: 14 strains available      Cell Lines: 0 lines available
Carrying any Ins2 Mutation:	93 strains or lines available

Original:	J:40063 Yoshioka M, et al., A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes. 1997 May;46(5):887-94
All:	395 reference(s)