These transgenic mice over-express the human ABCG5 and ABCG8 genes under the direction of their endogenous regulatory sequences. Copy number of the transgene was estimated using Southern blot analysis to compare transgenic mouse genomic DNA to human genomic DNA. These transgenic mice have approximately ten copies of the transgene. Northern blot analysis revealed the human transgene is expressed in the liver and small intestine. RT-PCR showed trace levels of transgene transcript in ovary tissue. Absorption of dietary cholesterol in transgenic mice is reduced by 50%. Mean fasting plasma cholesterol levels are significantly lower in female transgenic mice. Excretion of neutral sterols in feces is elevated to three times higher above normal in male transgenic mice and six times higher in female transgenic mice. Bile from transgenic animals is opaque as compared to the clear bile of wildtype animals. Cholesterol in the bile is elevated to levels five times higher than normal in male transgenic mice and seven times higher in female transgenic mice. The phospholipid level in the bile of male transgenic mice is slightly increased. When fed a high-cholesterol diet, transgenic mice did not exhibit any significant change in hepatic cholesterol levels. Genes encoding proteins involved in cholesterol synthesis are up regulated. Mice homozygous for the transgenic insert are viable and fertile. This mutant mouse strain may be useful in studies of cholesterol trafficking and cholesterol gallstone disease.

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These ABCG5/ABCG8 Tg mice express a transgene containing the human ABCG5 and ABCG8 genes, and exhibit reduced absorption of dietary cholesterol.

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