tailieunhanh - Báo cáo khoa học: Two CYP17 genes in the South African Angora goat (Capra hircus) – the identification of three genotypes that differ in copy number and steroidogenic output

In mammals, cytochrome P450 17a-hydroxylase⁄17–20 lyase (CYP17), which is encoded by a single gene, plays a critical role in the production of mineralocorticoids, glucocorticoids and androgens by the adrenal cortex. Two CYP17 isoforms with unique catalytic properties have been identified in the South African Angora goat (Capra hircus), a subspecies that is susceptible to cold stress because of the inability of the adrenal cortex to produce sufficient levels of cortisol. | ễFEBS Journal Two CYP17 genes in the South African Angora goat Capra hircus - the identification of three genotypes that differ in copy number and steroidogenic output Karl-Heinz Storbeck1 Amanda C. Swart1 Margaretha A. Snyman2 and Pieter Swart1 1 Department of Biochemistry University of Stellenbosch South Africa 2 Grootfontein AgriculturalDevelopment Institute Middelburg South Africa Keywords Angora goat copy number cortisol CYP17 cytochrome P450 17a-hydroxylase 17-20 lyase Correspondence P. Swart Department of Biochemistry University of Stellenbosch Private Bag X1 Matieland 7602 South Africa Fax 27 21 8085863 Tel 27 21 8085862 E-mail pswart@ Received 31 March 2008 revised 3 June 2008 accepted 4 June 2008 doi In mammals cytochrome P450 17a-hydroxylase 17-20 lyase CYP17 which is encoded by a single gene plays a critical role in the production of mineralocorticoids glucocorticoids and androgens by the adrenal cortex. Two CYP17 isoforms with unique catalytic properties have been identified in the South African Angora goat Capra hircus a subspecies that is susceptible to cold stress because of the inability of the adrenal cortex to produce sufficient levels of cortisol. A real-time-based genotyping assay was used in this study to identify the distribution of the two CYP17 alleles in the South African Angora population. These data revealed that the two CYP17 isoforms were not the product of two alleles of the same gene but two separate CYP17 genes encoding the two unique CYP17 isoforms. This novel finding was subsequently confirmed by quantitative real-time PCR. Goats were divided into three unique genotypes which differed not only in the genes encoding CYP17 but also in copy number. Furthermore in vivo assays revealed that the identified genotypes differed in their ability to produce cortisol in response to intravenous insulin injection. This study clearly demonstrates the presence of two CYP17 genes in the South African .