Mice homozygous for the Acc2^flox allele are viable, fertile, normal in size, and have no reported physical abnormalities. The Acc2^flox allele has loxP sites flanking the biotin-binding motif exon (and the preceding exon) of the targeted locus. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed sequences deleted in the cre-expressing cells/tissues. The exon immediately upstream of the biotin-binding catalytic domain was included so that splicing of the remaining exons following Cre-mediated deletion would introduce a frameshift and nonsense mutation after Asp865 in any translated protein. These mutant mice may be useful to generate conditional mutations for studying malonyl-CoA (the substrate for fatty acid synthesis and the regulator of fatty acid oxidation) synthesis and other metabolic cellular signaling molecules, as well as diet-induced obesity, glucose intolerance and insulin resistance.

NOTE: When these Acc2^flox mice are bred with germline cre-expressing mice (B6.FVB-Tg(Zp3-cre)3Mrt/J (Stock No. 003394)), the resulting offspring may be bred together to generate Acc2-deficient (Acc2KO) homozygous mice. Such pan Acc2KO homozygotes exhibit reduced total acetyl CoA carboxylase (ACC) activity in skeletal muscle, reduced heart size, decreased cardiac malonyl CoA levels, and a slight increase in energy expenditure (increased oxygen consumption during the dark cycle). Except for the increase in energy expenditure, this pan Acc2KO phenotype is similar to that reported for Acc2-deficient mice lacking exon 12 (Acacb^tm1Dejs; Hoehn et al., 2010 Cell Metab 11:70). However, the pan Acc2KO mice are not reported to display any of the abnormal metabolic effects described for Acacb^tm1Sjw homozygous mice (including reduced fat storage, continuous fatty acid oxidation, improved insulin sensitivity, and protection against obesity and diabetes induced by high-fat/high-carbohydrate diets) (Abu-Elheiga et al., 2001 Science 291:2613). Like the Acc2KO allele, the Acacb^tm1Sjw allele also lacks the biotin-binding domain. Unlike the Acc2KO allele, the Acacb^tm1Sjw allele retains the upstream exon (leaving the mutant RNA in-frame).