B6.Cg-Abca1^tm1Jp Abcg1^tm1Tall/J

Stock number: 021067
Product name: Abca1^fl Abcg1^fl
Research areas: Cardiovascular Research, Research Tools

Description

These Abca1^fl/fl Abcg1^fl/fl double floxed mice possess loxP sites flanking exons in the ATP-binding cassette, sub-family A (ABC1), member 1 (Abca1) gene and in the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene. This strain may be useful for studying cellular and plasma cholesterol homeostasis, and phospholipid transport.

Detailed description

These Abca1^fl/fl Abcg1^fl/fl double floxed mice possess loxP sites flanking exons 45-46 of the ATP-binding cassette, sub-family A (ABC1), member 1 (Abca1) gene and loxP sites flanking exon 3 of the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene. Two loxP-flanked neomycin resistance cassettes are still present in these mice, and the donating investigator reports that they do not effect protein expression in macrophages. ABCA1 controls the assembly of phospholipids and free cholesterol with lipid-free Apolipoprotein A-I (apoA-I) to form high density lipoprotein (HDL) and also mediates cholesterol efflux to apolipoproteins and small, pre-beta HDL particles from peripheral cells. Mutations in Abca1 are associated with Tangier disease and familial hypoalphalipoproteinemia, which are characterized by near absence of plasma HDL and the accumulation of cholesterol esters in tissues. ABCG1 is involved in cholesterol and phospholipid efflux to large, mature HDL particles, and regulates cellular lipid homeostasis. Mice that are homozygous for these alleles are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have Abca1 exons 45-46 and Abcg1 exon 3 deleted in cre-expressing tissues.

For example, when crossed to B6.129P2-Lyz2^tm1(cre)Ifo/J mice (Stock No. 004781) expressing Cre recombinase in the myeloid cell lineage, including monocytes, mature macrophages, and granulocytes, resulting mice display an increase in hematopoietic stem and multipotential progenitor cell (HSPC) mobilization and extramedullary hematopoiesis.

When crossed to C57BL/6J-Tg(Itgax-cre,-EGFP)4097Ach/J mice (Stock No. 007567) expressing Cre recombinase in dendritic cells, resulting mice display an increase in blood colony forming units, IL17 and IL23 secretion.

Development

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 of the ATP-binding cassette, sub-family A (ABC1), member 1 (Abca1) gene. 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. Resulting offspring were bred together to build a colony of Abca1^fl/fl mice. These mice were backcrossed to C57BL/6J mice for at least 12 generations.

Another targeting vector was designed to insert a single frt site and a single loxP site upstream of exon 3, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 3 of the ATP-binding cassette, sub-family G (WHITE), member 1 (Abcg1) gene. The construct was electroporated into B6(Cg)-Tyr^c-2J/J-derived ES cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with B6(Cg)-Tyr^c-2J/J females. Resulting offspring were bred together to build a colony of Abcg1^fl/fl mice. These mice were then bred to Abca1^fl/fl mice, and double floxed mice were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. The Tyr^c-2J gene was bred out of the colony.

Allele

Symbol: Abcg1^tm1Tall
Name: targeted mutation 1, Alan Tall
MGI accession ID: MGI:5450880
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Abcg1
Marker name: ATP binding cassette subfamily G member 1
Chromosome: 17
Strain of origin: C57BL/6
Molecular note: A targeting vector was designed to insert a single frt site and a single loxP site upstream of exon 3, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 3.

Allele

Symbol: Abca1^tm1Jp
Name: targeted mutation 1, John S Parks
MGI accession ID: MGI:3577723
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Abca1
Marker name: ATP-binding cassette, sub-family A (ABC1), member 1
Chromosome: 4
Strain of origin: 129S6/SvEvTac
Molecular note: LoxP sites were inserted to flank exons 45 and 46, which encode the second nucleotide-binding fold.