Intercrosses of miR-1-1 heterozygous mice revealed that approximately half of all miR-1-1 homozygous-null mice died before weaning when bred onto a pure 129 strain, similar to miR-1-2 null mice.
PDK1 has been shown to be oncogenic in Comma-1D mouse mammary epithelial cells, and Pten+/- tumor [ 40] formation was severely attenuated when bred with Pdpk1 hypomorphic mice that had only 10% of normal PDK1 enzyme activity.
When bred at 21°C, Elovl6 KO mice exhibited a 30% survival rate (χ2 p = 0.0003, n = 84); however, when housed at 24°C the Elovl6 KO mice had a normal Mendelian ratio (χ2 p = 0.110 n = 120).
When bred to homozygosity, Rps6kb1 floxed (S6K1fl/fl) mice were phenotypically indistinguishable from WT animals and displayed normal Rps6kb1 expression in the absence of cre-recombinase (data not shown).
Sall2-deficient mice were previously reported to have no apparent abnormal phenotype when bred on a C57BL/6 genetic background; however, a strain-specific incidence of neural tube defects and perinatal lethality were reported when bred on mixed genetic backgrounds.
Many of these mutations, when bred to homozygosity, however, are embryonic lethals in the mice.
Interestingly, these effects were abrogated when mice were bred in a cdk4−/− genetic background, demonstrating that AKT induces β-cell proliferation in a CDK4-dependent manner (Fatrai et al, 2006).
As Tek+/CreCD146floxed/floxe mice (CD146EC-KO mice) were viable, these mice were further bred to Tek+/+CD146floxed/floxed mice (WT mice), resulting in 50%% CD146EC-KO mice and 50 % WT mice, both of which were used for subsequent investigations (Fig. 1B).
However, in the present study, when these mice were bred to homozygosity, they developed a severe myopathic phenotype and died prematurely.
Strikingly, even when the mice were bred onto a uniform genetic background, the double mutants still showed a range of disease phenotypes.
