We previously described a lethal form of congenital adrenal hyperplasia(CAH) clinically identical and biochemically analogous to human congenital lipoid adrenal hyperplasia in a strain of rabbits due to SCC gene deletion. Thus, we cloned and sequenced the Wt rabbit SCC promoter and cDNA regions to construct the Wt SCC genes for future use in gene transfer study for CAH using the animal model as a prototype. The SCC promoter gene was isolated from a genomic library using a rabbit SCC 5'-cDNA probe for screening. The promoter DNA fragment was then subcloned into a Bluescript phagemid vector and sequenced. The SCC cDNA was isolated by screening the rabbit cDNA library generated from purified normal rabbit adrenal poly(A)+RNA. The sequence of the rabbit SCC cDNA clone (1.7 Kb) revealed the complete Wt rabbit SCC enzyme. The 1.7 Kb clone contained nine 5'-untranslated nucleotides, 148 3'-untranslated nucleotides including poly(A) tail, and an open reading frame of 1557 nucleotides which includes a 5' cap and stop codon. The encoded rabbit P450 SCC cDNA contained 518 amino acids. Compared to the human cDNA, the coding region of the rabbit SCC cDNA was 9 bp less than the human SCC cDNA, 81% identical in nucleotides sequence and 77.4% identical in amino acid sequence to the human SCC cDNA, and had higher sequence homology to the human SCC cDNA than other species. The sequence of a 5'-flanking genomic clone (1.2 Kb) revealed the sequence of a known 5' region of the SCC cDNA which identified a transcription initiation site, exon I, and a promoter region of 901 bp upstream from the transcription initiation site. The TATA box sequence was located at -68 bp from the initiation codon and a CAT box was not found. The TATA box in the SCC promoter region in other species reported by others were at -70 bp in the mouse, at -82 bp in the bovine, and at -91 bp in the human. The CAT box was reported only in the human SCC gene. The nucleotide sequence of the promoter region was 26-27% identical to humans and other species. In vitro activity of the cloned SCC genes are under way for future application in the development of a gene transfer technique using the animal CAH model.