B6.129P2-Abcg5^tm1Plo/J

Stock number: 008235
Research areas: Cardiovascular Research, Hematological Research, Internal/Organ Research, Metabolism Research, Reproductive Biology Research, Research Tools

Description

These Abcg5-mutant mice harbor an IRES-LacZ-PGKneo disruption of the adenosine triphosphate-binding cassette (ABC) half-transporter G5 (Abcg5) locus and may be useful in studying sitosterolemia and macrothrombocytopenia, absorption/secretion of plant sterols and cholesterol (hepatic and intestinal), megakaryocyte development, and the relationship between hematological dysfunction and disturbed sterol metabolism.

Detailed description

Mice homozygous for this adenosine triphosphate-binding cassette (ABC) half-transporter G5 mutant allele (Abcg5^-/-) are viable and severely subfertile; the donating investigator reports that males have significantly reduced fertility and females are almost non-fertile. No gene product (mRNA) from the mutant allele is detected in homozygous liver extracts. The expression of beta-galactosidase (lacZ) from the targeted gene is not characterized to date (July 2008). Abcg5-deficient mice exhibit sitosterolemia (high plasma plant sterol concentrations) and macrothrombocytopenia (enlarged platelets caused by defective megakaryocyte development) associated with a near 70% reduction in total number of platelets. Specifically, when allowed ad libitum access to PicoLab Rodent Diet 5053 chow, homozygous mice exhibit strongly elevated plasma levels of β-sitosterol (37-fold) and campesterol (7.7-fold); with further increased levels upon addition of the synthetic Liver-X Receptor agonist T0901317. Homozygotes also exhibit reduced plasma cholesterol concentrations, reduced hepatic expression of the closely related ABC half-transporter G8 (Abcg8), and normal cholesterol secretion into the bile. These Abcg5-mutant mice may be useful in studying sitosterolemia and macrothrombocytopenia, absorption / secretion of plant sterols and cholesterol (hepatic and intestinal), megakaryocyte development, and the relationship between hematological dysfunction and disturbed sterol metabolism.

Of note, These Abcg5-mutant mice may also be used in conjunction with other ABC sub-family G mutant strains including G5G8 double mutant mice (Stock No. 004670) and mice bearing a human ABCG5/ABCG8 transgene (Stock No. 004583).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these Abcg5-mutant mice could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace an 87-bp fragment corresponding to a segment of exon 3 (encoding the 29 amino acids region containing the conserved adenosine triphosphate-binding cassette signature motifs located in the N-terminal region of the protein) of the targeted gene with an internal ribosomal entry site, beta-galactosidase (lacZ) cDNA, PGK-neomycin resistance cassette, and polyA sequence. This construct was electroporated into "129/OlaHsd"-derived embryonic stem (ES) cells and chimeric mice were used for generation of mutant animals on a "C57BL/6Jx129/OlaHsd" genetic background. These Abcg5-mutant mice were then backcrossed to C57BL/6J inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, these mice may have been bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Abcg5^tm1Plo
Name: targeted mutation 1, Torsten Ploesch
MGI accession ID: MGI:2687002
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Abcg5^-
Marker symbol: Abcg5
Marker name: ATP binding cassette subfamily G member 5
Marker synonyms: cmp; Sterolin-1; STSL; STSL2; tac; trac
Chromosome: 17
Strain of origin: 129P2/OlaHsd
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: Expression of lacZ has not been characterized (July, 2008)
Molecular note: The endogenous locus was disrupted by the insertion of a cassette containing beta galactosidase and neo into exon 3. The insertion deleted 87 bp.