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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Type Mutant Strain; Transgenic; Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N50+N1F4 (05-DEC-06) Donating Investigator Paul Epstein, University of Louisville Description
Transgenic mice are viable, display small eyes with cataracts and are hyperglycemic within 24 hours of age. S1 Nuclease protection assays indicate expression of calmodulin in the pancreas of 40-60 day old transgenic mice. Immunofluorescence analysis of the pancreas indicates increased levels of camodulin in B-cells of the pancreas. Camodulin fluorescing cells were not detected in the pancreatic acinar cells or any other tissue. Digital image scanning indicates the concentration of camodulin in transgenic B-cells is 5-fold higher than in wild type controls. Pancreatic insulin is 28% of control levels by 15 days of age. Insulin mRNA levels were also reduced in the transgenic animals. Transgenic mice experience hypoalbuminemia, elevated blood pressure, impaired cardiomyocytes and late stage diabetic nephropathy. Although transgenic mice are hyperglycemic within 24 hours of age, they are able to survive over a year without insulin treatment.This stock is useful for studying systemic complications related to type 1 diabetes.
Development
FVB(Cg)-Tg(Ins2-CALM)26OveTg(Cryaa-Tag)1Ove/PneJ expresses a chicken calmodulin minigene (CALM1) controlled by the rat insulin II promoter (Ins2)(Referred to as BIC). In addition, these mice express a truncated SV40 T antigen (TAg) controlled by a lens specific alpha A crystallin (Cryaa) promoter (referred to as GR19). These transgenes were first co-inserted by Epstein et, al., (1989) into FVB oocytes. Transgenic founders carrying both genes were mated to FVB and found to co-segregate (Epstein et al, 1989). This stock was maintained on an FVB background until 1989 when it was backcrossed to CD-1. Since 1993 this stock has been backcrossed to FVB for 20+ generations. In 2005, The Jackson Laboratory received FVB(Cg)-Tg(Ins2-CALM)26OveTg(Cryaa-Tag)1Ove/PneJ hemizygous animals at generation N50.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Cryaa
002489 CBA/CaGnLe-Cryaalop18/J View Strains carrying other alleles of Cryaa (1 strain)
008215 (C57BL/6-Tg(TRAMP)8247Ng/J X FVB/NJ)F1/J 003382 B10.D2-Tg(C3-1-TAg)cJeg/J 008247 B6.Cg-Tg(Ela1-TAg*)289Mjt/J 003380 B6.FVB-Tg(C3-1-TAg)cJeg/J 003135 C57BL/6-Tg(TRAMP)8247Ng/J 003445 C57BL/6J-Tg(Amy1TAg)354Knw/J 003446 C57BL/6J-Tg(Amy1TAg)501Knw/J 002233 C57BL/6J-Tg(SV)7Bri/J 003189 C57BL/6J-Tg(WAPTAg)3Knw/J 003188 C57BL/6J-Tg(WapTAg)1Knw 003381 FVB-Tg(C3-1-TAg)cJeg/J 002380 NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ 002033 NOD/ShiLt-Tg(RipTAg)1Lt/J
Additional Web Information
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
Related Disease (OMIM) Terms
Diabetes Mellitus, Insulin-Dependent; IDDM Mammalian Phenotype Terms assigned by genotype
Tg(Cryaa-TAg)1Ove/0 Tg(Ins2-CALM1)26Ove/0
FVB/N
- homeostasis/metabolism phenotype
- decreased circulating insulin level (MGI Ref ID J:97926)
- markedly lower serum insulin levels
- hyperglycemia (MGI Ref ID J:97926)
- increased circulating glucagon level (MGI Ref ID J:97926)
- elevated serum glucagon levels
- increased urine glucose level (MGI Ref ID J:97926)
- renal/urinary system phenotype
- increased urine glucose level (MGI Ref ID J:97926)
- digestive/alimentary phenotype
- decreased insulin secretion (MGI Ref ID J:97926)
- reduced pancreatic insulin levels; early onset and increased severity with age
- pancreatic insulin content was 28% of control levels
- insulin mRNA levels were also reduced
- decreased pancreatic beta cell number (MGI Ref ID J:97926)
- the number of beta cells per islet was reduced
- endocrine/exocrine gland phenotype
- decreased insulin secretion (MGI Ref ID J:97926)
- reduced pancreatic insulin levels; early onset and increased severity with age
- pancreatic insulin content was 28% of control levels
- insulin mRNA levels were also reduced
- decreased pancreatic beta cell number (MGI Ref ID J:97926)
- the number of beta cells per islet was reduced
Research Applications
This mouse can be used to support research in many areas including:
TAg relatedCardiovascular Research
Hypertension
Developmental Biology Research
Eye Defects
Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Apoptosis Research
Extracellular Modulators
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Cryaa-TAg)1Ove | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Paul Overbeek | ||
| Common Name(s) | GR19; | ||
| Mutation Made By | Paul Overbeek, Baylor College of Medicine | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | TAg, SV40 large T-antigen, SV40 | ||
| Simian virus 40 T antigen (SV40Tag) is a multifunctional regulatory protein that stimulates gene transcription and forms complexes with cell cycle-regulatory proteins such as Trp53 and Rb1 that are implicated in human breast cancer. | |||
| Promoter | Cryaa, crystallin, alpha A, mouse, laboratory | ||
| General Note | Cataracts induced by the expression of this transgene have been used as an obvious visible marker for the presence of coinjected transgenes. | ||
| Molecular Note | This transgene expresses a truncated form of the SV40 large T antigen under the control of the mouse Cryaa promoter. This promoter is lens-specific. [MGI Ref ID J:97926] | ||
| Allele Symbol | Tg(Ins2-CALM1)26Ove | ||
| Allele Name | transgene insertion 26, Paul Overbeek | ||
| Common Name(s) | BamInsCam; Bic; CaMTg; OVE26; | ||
| Mutation Made By | Paul Overbeek, Baylor College of Medicine | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | CALM1, calmodulin 1, chicken | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | This transgene expresses a chicken calmodulin gene under the control of rat insulin II promoter. This promoter drives expression in pancreatic beta cells. [MGI Ref ID J:97926] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
References
References
Additional References
Tg(Cryaa-TAg)1Ove related
Epstein PN; Overbeek PA; Means AR. 1989. Calmodulin-induced early-onset diabetes in transgenic mice. Cell 58(6):1067-73. [PubMed: 2673540] [MGI Ref ID J:97926]Tg(Ins2-CALM1)26Ove related
Carlson EC; Audette JL; Klevay LM; Nguyen H; Epstein PN. 1997. Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice. Anat Rec 247(1):9-19. [PubMed: 8986297] [MGI Ref ID J:37570]Carlson EC; Audette JL; Veitenheimer NJ; Risan JA; Laturnus DI; Epstein PN. 2003. Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice. Anat Rec A Discov Mol Cell Evol Biol 271(2):332-41. [PubMed: 12629676] [MGI Ref ID J:105967]
Corrons FJ; Camihort GA; Gomez Dumm CL; Epstein PN; Gagliardino JJ. 1996. [Structure and ultrastructure of the endocrine pancreas in diabetic transgenic mice] Medicina (B Aires) 56(6):666-70. [PubMed: 9284569] [MGI Ref ID J:97921]
Duan J; Zhang HY; Adkins SD; Ren BH; Norby FL; Zhang X; Benoit JN; Epstein PN; Ren J. 2003. Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice: role of Akt and RhoA. Am J Physiol Endocrinol Metab 284(2):E366-76. [PubMed: 12531745] [MGI Ref ID J:97919]
Epstein PN; Boschero AC; Atwater I; Cai X; Overbeek PA. 1992. Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes. Proc Natl Acad Sci U S A 89(24):12038-42. [PubMed: 1465437] [MGI Ref ID J:97924]
Epstein PN; Overbeek PA; Means AR. 1989. Calmodulin-induced early-onset diabetes in transgenic mice. Cell 58(6):1067-73. [PubMed: 2673540] [MGI Ref ID J:97926]
Epstein PN; Ribar TJ; Decker GL; Yaney G; Means AR. 1992. Elevated beta-cell calmodulin produces a unique insulin secretory defect in transgenic mice. Endocrinology 130(3):1387-93. [PubMed: 1371447] [MGI Ref ID J:97925]
Gomez Dumm CL; Atwater I; Epstein PN; Gagliardino JJ. 1994. Quantitative immunocytochemical study of islet cell populations in diabetic calmodulin-transgenic mice. Virchows Arch 425(1):73-7. [PubMed: 7921417] [MGI Ref ID J:97923]
Gu H; Epstein PN; Li L; Wurster RD; Cheng ZJ. 2008. Functional changes in baroreceptor afferent, central and efferent components of the baroreflex circuitry in type 1 diabetic mice (OVE26). Neuroscience 152(3):741-52. [PubMed: 18328631] [MGI Ref ID J:135406]
Liang Q; Carlson EC; Donthi RV; Kralik PM; Shen X; Epstein PN. 2002. Overexpression of metallothionein reduces diabetic cardiomyopathy. Diabetes 51(1):174-81. [PubMed: 11756338] [MGI Ref ID J:73761]
Ribar TJ; Epstein PN; Overbeek PA; Means AR. 1995. Targeted overexpression of an inactive calmodulin that binds Ca2+ to the mouse pancreatic beta-cell results in impaired secretion and chronic hyperglycemia. Endocrinology 136(1):106-15. [PubMed: 7828519] [MGI Ref ID J:22635]
Shen X; Zheng S; Metreveli NS; Epstein PN. 2006. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes 55(3):798-805. [PubMed: 16505246] [MGI Ref ID J:106851]
Shen X; Zheng S; Thongboonkerd V; Xu M; Pierce WM Jr; Klein JB; Epstein PN. 2004. Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes. Am J Physiol Endocrinol Metab 287(5):E896-905. [PubMed: 15280150] [MGI Ref ID J:95399]
Thongboonkerd V; Barati MT; McLeish KR; Benarafa C; Remold-O'Donnell E; Zheng S; Rovin BH; Pierce WM; Epstein PN; Klein JB. 2004. Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis. J Am Soc Nephrol 15(3):650-62. [PubMed: 14978167] [MGI Ref ID J:97915]
Thongboonkerd V; Barati MT; McLeish KR; Pierce WM; Epstein PN; Klein JB. 2004. Proteomics and diabetic nephropathy. Contrib Nephrol 141:142-54. [PubMed: 14650230] [MGI Ref ID J:97916]
Tsunekawa S; Miura Y; Yamamoto N; Itoh Y; Ariyoshi Y; Senda T; Oiso Y; Niki I. 2005. Systemic administration of pituitary adenylate cyclase-activating polypeptide maintains beta-cell mass and retards onset of hyperglycaemia in beta-cell-specific calmodulin-overexpressing transgenic mice. Eur J Endocrinol 152(5):805-11. [PubMed: 15879367] [MGI Ref ID J:97914]
Ye G; Metreveli NS; Donthi RV; Xia S; Xu M; Carlson EC; Epstein PN. 2004. Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. Diabetes 53(5):1336-43. [PubMed: 15111504] [MGI Ref ID J:89389]
Ye G; Metreveli NS; Ren J; Epstein PN. 2003. Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production. Diabetes 52(3):777-83. [PubMed: 12606520] [MGI Ref ID J:97918]
Yu W; Niwa T; Miura Y; Horio F; Teradaira S; Ribar TJ; Means AR; Hasegawa Y; Senda T; Niki I. 2002. Calmodulin overexpression causes Ca(2+)-dependent apoptosis of pancreatic beta cells, which can be prevented by inhibition of nitric oxide synthase. Lab Invest 82(9):1229-39. [PubMed: 12218084] [MGI Ref ID J:97920]
Zhang X; Ye G; Duan J; Chen AF; Ren J. 2003. Influence of gender on intrinsic contractile properties of isolated ventricular myocytes from calmodulin-induced diabetic transgenic mice. Endocr Res 29(2):227-36. [PubMed: 12856810] [MGI Ref ID J:97917]
Zheng S; Noonan WT; Metreveli NS; Coventry S; Kralik PM; Carlson EC; Epstein PN. 2004. Development of late-stage diabetic nephropathy in OVE26 diabetic mice. Diabetes 53(12):3248-57. [PubMed: 15561957] [MGI Ref ID J:94602]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number FGB29
Colony Maintenance
Breeding & Husbandry This stock is genotyped by phenotype (small eyes with cataracts and excessive urination). Due to early diabetes onset this stock breeds poorly. Transgenic males (hemizygote) lose fertility around 6 months of age and are maximally fertile between 75 to 125 days of age. Transgenic females (hemizygote) are highly non-productive. Transgenic females which become preg need to have their litters fostered as the the pups are unthrifty or die otherwise. Females that do become pregnant become non-productive after 120 days of age. Transgenic mice are shipped with Water Transit Kits after 3-4 days of acclimation, as the majority of animals shipped using Napa Nectar have arrived dead or in poor condition.
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $100.00 Female or Male Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $114.60 FVB/NJ (001800) x Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove $152.25 Noncarrier, Noncarrier x Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $130.00 Female or Male Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $149.00 FVB/NJ (001800) x Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove $198.00 Noncarrier, Noncarrier x Hemizygous for Tg(Ins2-CALM1)26Ove, Hemizygous for Tg(Cryaa-TAg)1Ove
Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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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 and Purchasing Information
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