These mice possess loxP sites flanking exon 2 of the acyl-CoA synthetase long-chain family member 1 (Acsl1) gene and have applications in studies related to lipid metabolism and signaling, energy metabolism, and cardiac function.
Rosalind Coleman, University of North Carolina
The isozyme encoded by the acyl-CoA synthetase long-chain family member 1 (Acsl1) gene catalyzes the synthesis of acyl-CoA from fatty acids that are between 10 and 22 carbons in size. These mice possess loxP sites on either side of exon 2 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.
When bred to a strain with Cre recombinase expression in the liver (see Stock No. 003574 for example), the resulting mutant mouse strain exhibits a 50% decrease in total hepatic acyl-CoA synthetase enzyme activity and may be useful in studies of lipid metabolism and liver physiology.
When bred to a strain with Cre recombinase expression in adipose tissue (see Stock No. 005069 for example), the mutant mice exhibit a 80% decrease of total acyl-CoA synthetase activity in adipose tissue, marked deficiency of adipose tissue to oxidize fatty acids, and impaired thermogenesis.
When bred to a strain with tamoxifen-mediated Cre recombinase expression in heart (see Stock No. 005657 and Stock No. 005650, for examples), the mutant mice have a 90% decrease of total acyl-CoA synthetase activity in heart ventricles, and exhibit cardiac hypertrophy and diastolic dysfunction.
A targeting vector containing FRT site flanked MC1-Neo selection cassette was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted downstream of exon 2. This construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells which were transiently transfected with a FLP1 (flpE) recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 7 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Rosalind Coleman|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Acsl1, acyl-CoA synthetase long-chain family member 1|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A loxP site and FRT flanked MC1-neo cassette were inserted 5' to exon 2 and an additional loxP site was placed immediately 3' of exon 2. The neomycin cassette was then excised by transient expression of Flpe recombinase. Cre expression in the liver of homozygous mice eliminates most mRNA for this gene.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Acsl1flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #019360 in your Materials and Methods section.