title: Nucleotide sequence analysis of murine 21-hydroxylase genes: mutations affecting gene expression.
abstract: Steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10] is a cytochrome P-450 enzyme required for the adrenal synthesis of mineralocorticoids and glucocorticoids. The gene encoding this protein is present in two copies (21-OHase A and B) in the S region of the murine major histocompatibility complex. Previous studies utilizing gene-specific oligonucleotide probes and gene transfer showed that only the 21-OHase A gene is expressed in the BALB/c mouse. Here, we present the complete primary structures of both BALB/c 21-OHase encoding genes. Comparison of the nucleotide sequences defines a deletion of 215 nucleotides spanning the second exon of the 21-OHase B gene; other nucleotide changes in the 21-OHase B gene introduce frame shifts and premature termination codons. Southern blot analysis of C57BL/6 and DBA/2J mice indicates that a similar deletion is present in these strains; however the C3H/HeJ strain is a structural variant. A hybrid gene composed of the 21-OHase B promoter placed 5' of the 21-OHase A structural sequences was efficiently transcribed following transfection into Y1 adrenocortical tumor cells. These findings demonstrate that the 21-OHase B gene promoter is functional and suggest that mutations within the 21-OHase B structural gene are responsible for its lack of expression.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002872:Chromosome Deletion; D005786:Gene Expression Regulation; D005796:Genes; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase