Expression of the human cholesterol 7alpha-hydroxylase gene in transgenic mice.

We have generated transgenic mice expressing human CYP7A1 transgenes. Only 1.5 kilobases (kb) of 5' upstream sequence and 6.5 kb of 3' sequence were sufficient for hepatic transcription of the transgenes. However, the 5' end segment alone was not sufficient to direct liver expression, suggesting that additional hepatic regulatory elements reside in the 3' extension or within introns. The level of expression of these transgenes was low in comparison to the levels of the endogenous mouse CYP7A1 mRNA. To generate mice expressing higher levels of CYP7A1 mRNA, we injected a large human genomic PAC clone, extending up to -105 kb 5' of the structural gene and about 50 kb 3' of the gene. These transgenic mice expressed CYP7A1 mRNA at higher levels, suggesting that additional hepatic regulatory elements are found either 5' of -1520 or beyond 6.5 kb 3' of the gene.