These Abcg5 and Abcg8 knock-out mice exhibit increased fractional absorption of dietary plant sterols resulting in elevated plasma sitosterol levels.
Helen H. Hobbs, UT Southwestern Medical Center
Mice that are homozygous for this targeted allele are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected in liver or jejunum. A 2 to 3 fold increase in fractional absorption of dietary plant sterols results in plasma sitosterol levels that are elevated 30 fold compared to wildtype levels. Biliary cholesterol levels are low, as are plasma and liver cholesterol levels. Plasma and liver cholesterol levels increase rapidly (2.4 and 18 fold, respectively) following cholesterol feeding. This mutant mouse strain represents a model that may be useful in studies related to sitosterolemia and cholesterol homeostasis.
The mouse Abcg5 and Abcg8 genes lie in a head-to-head configuration, separated by approximately 400 bp. A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt Abcg5 exons 1 - 2, Abcg8 exons 1 - 3 and the sequence that lies between the two genes. The neomycin resistance gene is flanked by both loxP and FRT (FLP recombinase target sequence) sites. The construct was electroporated into 129S6/SvEv-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were bred by the Donating Investigator to C57BL/6J once before making the line homozygous.
|Allele Name||targeted mutation 1, Helen H Hobbs|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Abcg5/Abcg8tm1Hobb; G5G8-|
|Gene Symbol and Name||Del(17Abcg5-Abcg8)1Hobb, deletion, Chr 17, Helen H Hobbs 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Both the Abcg5 and Abcg8 endogenous loci, which are oriented head to head and separated by approximately 400 bp, were disrupted by the integration of a single targeting construct. A neomycin selection cassette flanked by both loxP and frt sites replaced sequence extending from Abcg5 intron 2 into Abcg8 intron 3. The Walker A consensus sequences that make up a portion of the ATP binding sites in both genes were deleted. Northern and Western blot analyses indicated an absence of normal transcript and protein derived from both loci in homozygous mutant mice.|
|Mutations Made By|| |
Liqing Yu, Wake Forest Univ. School of Medicine
When maintaining a live colony, these mice are bred mating heterozygote females to homozygote males. Homozygous breeder pair matings have been found to be unproductive by The Jackson Laboratory colony managers (February 3, 2005).
When using the G5G8- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004670 in your Materials and Methods section.