title: Genetic contributions to the variation among rabbits of liver microsomal deoxycorticosterone synthesis.
abstract: Outbred New Zealand white rabbits exhibit two phenotypes, 21H and 21L, corresponding to rates greater than or less than 1 nmol/min/mg, respectively, for liver microsomal progesterone 21-hydroxylase activity. In contrast, the inbred strain III/J exhibits only the 21L phenotype. Two 21H male New Zealand white rabbits were mated with several female III/J rabbits to produce a total 46 progeny. Both the 21H and 21L phenotypes were evident among male and female offspring in roughly equal numbers. Backcrosses between 21L progeny and III/J rabbits exhibit only the 21L phenotype, whereas 21H offspring yield both 21H and 21L progeny when backcrossed to the 21L inbred strain III/J. These results are consistent with autosomal dominant inheritance of the 21H phenotype. Analysis of Southern blots of genomic DNA digested with the restriction endonuclease KpnI reveals 20-, 13-, and 9-kb fragments that hybridize with a probe derived from the 3'-untranslated region of the 21-hydroxylase cDNA. The 13-kb band is not observed for strain III/J or 21L progeny of strain III/J crossed with 21H rabbits, but it is detected for both 21H fathers and 21H progeny indicating that the genetically determined difference of 21-hydroxylase expression is inherited cis to the gene for P450IIC5, the hepatic progesterone 21-hydroxylase. Electrophoretic analysis of P450IIC5 synthesized in vitro from mRNA isolated from 21L and 21H rabbits reveals that little or no P450IIC5 is synthesized from 21L mRNAs. A second immunoreactive, electrophoretically distinct protein is synthesized from both 21L and 21H mRNAs to a similar extent but in lesser amounts than P450IIC5. The second protein could represent either an allozymic form of the enzyme or the product of a distinct locus. Thus, it is likely that distinct structural genes for P450IIC5 contribute to the differences in P450-mediated metabolism in 21L as compared to 21H rabbits.
authors.affiliation: Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, California 92037.
authors.forename: E F
authors.initials: EF
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Finlayson
authors.forename: C M
authors.initials: CM
authors.lastname: Hujsak
authors.forename: U R
authors.initials: UR
authors.lastname: Pendurthi
authors.forename: R H
authors.initials: RH
authors.lastname: Tukey
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D003900:Desoxycorticosterone / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003900:Desoxycorticosterone; D004247:DNA; D013255:Steroid 21-Hydroxylase; D004262:DNA Restriction Enzymes