The Cre-loxP site-specific recombination system is a useful tool to manipulate genomic sequences. To produce conditional activation or inactivation of genes in mice by the Cre-loxP system, it is necessary to express Cre recombinase in tissue-specific or developmental regulated manners. We used human muscle-specific actin promoters to control Cre-expression. Mammalian cells have at least six actin-isoform genes, four of which are musclespecific, and subdivided into two smooth-muscle actins and two striated-muscle actins (Miwa et al., 1991). We employed human smooth muscle α-actin (SmαA) and cardiac α-actin (CaαA) promoters from each subgroup.

The SmαA gene expresses predominantly in aortic tissues and the CaαA gene does in the heart. In the human SmαA promoter, not only the 5! upstream but also the first intron regions are necessary to direct transcription in smooth-muscle cell lineage-restricted fashion (Kawada et al., 1999). The 4.7-kb fragment from J891 to+ 3828 of the SmαA gene (Nakano et al., 1991)