Exons 45 and 46 of the mouse Abca1 gene are flanked by loxP sites in this conditional targeted mutant strain. Cre-mediated excision of the floxed region results in a knockout allele.
John Parks, Wake Forest University School of Medicine
Patients with Tangier disease exhibit extremely low plasma HDL concentrations resulting from mutations in the ATP-binding cassette, sub-family A, member 1 (ABCA1) protein. ABCA1 controls the rate-limiting step in HDL particle assembly by mediating efflux of cholesterol and phospholipid from cells to lipid-free apoA-I, which forms nascent HDL particles.
Exons 45 and 46 of the mouse Abca1 gene, encoding the second nucleotide-binding domain, are flanked by loxP sites in this conditional targeted mutant strain. Cre-mediated excision of the floxed region results in a knockout allele.
Homozygous deletion mice generated through crosses with liver-specific Alb-Cre animals (see Stock No. 003574) have total plasma and HDL cholesterol concentrations that are 19% and 17% those of wildtype littermates, respectively. Western blot analysis of liver membranes from homozygous knockout mice indicated near undetectable levels of ABCA1.
A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 45, and a single loxP site downstream of exon 46. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. This strain was backcrossed to C57BL/6 mice (substrain uncertain) for many generations. A 272 SNP scan carried out by the donating lab indicates a background that is approximately 94-97% C57BL/6-like.
|Allele Name||targeted mutation 1, John S Parks|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Abca1fl; Abca1flox|
|Gene Symbol and Name||Abca1, ATP-binding cassette, sub-family A (ABC1), member 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||LoxP sites were inserted to flank exons 45 and 46, which encode the second nucleotide-binding fold.|
Homozygotes and heterozygotes are viable and fertile.
When using the Abca1fl mouse strain in a publication, please cite the originating article(s) and include JAX stock #028266 in your Materials and Methods section.