Transgenic mice develop severe diabetes within hours of birth. The diabetes is progressive and characterized by elevated blood glucose and glucagon that coincides with reduced serum and pancreatic insulin. There is a 5-fold increase in the content of calmodulin and its mRNA in beta cells of the pancreas. This stock is useful for studying systemic complications related to type 1 diabetes.
Paul N. Epstein, University of Louisville
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.
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.
|Expressed Gene||CALM1, calmodulin 1, chicken|
|Site of Expression|
|Allele Name||transgene insertion 26, Paul Overbeek|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Allele Synonym(s)||BamInsCam; Bic; CaMTg; OVE26|
|Gene Symbol and Name||Tg(Cryaa-TAg,Ins2-CALM1)26Ove, transgene insertion 26, Paul Overbeek|
|Promoter||Ins2, insulin 2, rat|
|Expressed Gene||CALM1, calmodulin 1, chicken|
|Strain of Origin||FVB/N|
|Molecular Note||A transgene expressing chicken calmodulin gene under the control of pancreatic beta cell-specific rat insulin II promoter was coninjected with a transgene expressing a truncated form of the SV40 large T antigen under the control of the lens-specific mouse Cryaa promoter. Lines 26 and 29 express both transgenes.|
|Mutations Made By|| |
Paul Overbeek, Baylor College of Medicine
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 six 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 pregnant need to have their litters fostered as the pups are unthrifty or die otherwise. Females that do become pregnant become non-productive after 120 days of age.
When using the OVE26 mouse strain in a publication, please cite the originating article(s) and include JAX stock #005564 in your Materials and Methods section.
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