Double mutant, Apoe-null, Akita heterozygous, mice may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, hypercholesterolemia, and diabetes-related macrovascular complications.
T1DR Colony, The Jackson Laboratory
Mice homozygous for the Akita spontaneous mutation are stunted and typically die postnatally 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). Apoe-null homozygotes have marked increase in total plasma cholesterol levels that are unaffected by age or sex (see the datasheet for Stock No. 002052 for additional information).
These double mutant mice (Apoe-null, Akita heterozygous) may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, hypercholesterolemia, and diabetes-related macrovascular complications.
B6-Apoe, Stock No. 002052 - B6.129P2-Apoetm1Unc/J, mutant mice were mated with B6-Akita, Stock No. 003548- C57BL/6-Ins2Akita/J. Apoe and Ins2 are both located on Chr. 7. Mice heterozygous for the Apoe and Ins2Akita mutations were mated to mice homozygous for the Apoe mutation. Mice were identified with the required recombination event producing offspring homozygous for the Apoe and heterozygous for Ins2Akita mutations. In 2011, this strain was transferred to the repository at generation N2F1p+N1.
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||AopE(-); apoE-; APOE KO; Apoetm1Un; apoE0; ApoE-KO; EKO; epsilon-; mE-; mEKO|
|Gene Symbol and Name||Apoe, apolipoprotein E|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3 of the Apoe gene. Plasma from homozygous mutant mice gave no detectable immunoprecipitate by the Ouchterlony double immunodiffusion test using a rabbit antibody to rat APOE.|
|Mutations Made By|| |
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
|Allele Synonym(s)||Akita; AkitaIns2; Ins2C96Y; Ins2Mody; Mody; Mody4|
|Gene Symbol and Name||Ins2, insulin II|
|Strain of Origin||C57BL/6NSlc|
|Molecular Note||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.|