Mice that are homozygous for this Abcg8 (ATP-binding cassette, sub-family G (WHITE), member 8) targeted mutation exhibit increased plasma and tissue levels of sitosterol and campesterol (plant sterols) and infertility if not maintained on a plant sterol free diet. This mutant mouse strain may be useful in studies of sitosterolemia and phytosterolemia.
Shailendra B Patel, Medical College of Wisconsin
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Female homozygotes are infertile, and male homozygotes exhibit rare infertility, if not maintained on a plant sterol free diet or with drug treatment to block uptake of plant sterols. No gene product (mRNA) is detected by Northern blot and RT-PCR analysis of total hepatic RNA from homozygous animals. Homozygotes have increased plasma and tissue levels of sitosterol and campesterol (plant sterols) with impaired cholesterol secretion in bile. Expression of Abcg5 (ATP-binding cassette, sub-family G (WHITE), member 5) is unchanged in homozygotes. Liver cholesterol levels in homozygotes is decreased by approximately 50%. Serum cholesterol levels are decreased by 52% in homozygotes and 26% in heterozygotes. Heterozygotes exhibit an intermediate phenotype with decreased biliary sterol secretion but do not become sitosterolemic. This mutant mouse strain may be useful in studies of sitosterolemia and phytosterolemia.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt parts of exons 3 and 4 and normal splicing. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells (as reported by the Donating Investigator). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. Heterozygotes were intercrossed to generate homozygotes and the mice were then backcrossed to C57BL/6J for 17 generations.
|Allele Name||targeted mutation 1, Eric L Klett|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Abcg8/sterolin2; Abcg8-|
|Gene Symbol and Name||Abcg8, ATP binding cassette subfamily G member 8|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Part of exon 3 through part of exon 4 was replaced by a neomycin resistance cassette resulting in disruption of the ABC Walker A motif. No transcription was detected by Northern blot analysis.|
|Mutations Made By|| |
Shailendra Patel, Medical College of Wisconsin
When maintaining a live colony, these mice can be bred as homozygotes if maintained on a plant sterol free diet or with drug treatment to block uptake of plant sterols. Homozygous mice on a regular diet exhibit female infertility and rare male infertility.
When using the B6.129-Abcg8tm1Elk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008763 in your Materials and Methods section.