B6.Cg-Apoe^tm1Unc Ins2^Akita/J

Stock number: 013040
Product name: B6-ApoE, Akita
Research areas: Cardiovascular Research, Cell Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Mouse/Human Gene Homologs

Description

Double mutant, Apoe-null, Akita heterozygous, mice may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, hypercholesterolemia, and diabetes-related macrovascular complications.

Detailed description

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.

Development

B6-Apoe, Stock No. 002052 - B6.129P2-Apoe^tm1Unc/J, mutant mice were mated with B6-Akita, Stock No. 003548- C57BL/6-Ins2^Akita/J. Apoe and Ins2 are both located on Chr. 7. Mice heterozygous for the Apoe and Ins2^Akita 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 Ins2^Akita mutations. In 2011, this strain was transferred to the repository at generation N2F1p+N1.

Allele

Symbol: Ins2^Akita
Name: Akita
MGI accession ID: MGI:1857572
Generation method: Spontaneous
Marker symbol: Ins2
Marker name: insulin II
Chromosome: 7
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.

Allele

Symbol: Apoe^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857129
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
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.