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.
