title: SF1 polymorphisms in the mouse and steroidogenic potential.
abstract: ACTH-resistance in four mutant derivatives of a mouse adrenocortical tumor cell line results from a defect that reduces the activity of steroidogenic factor-1 (SF1) thereby preventing expression of the ACTH receptor and other SF1-dependent genes. The SF1 genes from these mutants contain a sequence difference that changes an Ala to Ser at codon 172. Steroidogenic factor-1(S172) represents a polymorphism rather than a spontaneous mutation since the two forms of SF1, SF1(A172), and SF1(S172), can be traced to the hybrid mouse strain (C57L/J x A/HeJ) from which the original adrenal tumor was derived. The SF1(S172) allele is amplified in three of the four mutant clones together with the neighboring genes germ cell nuclear factor and LIM homeobox2. The two forms of SF1 had only modest differences in transcriptional activity in reporter gene assays, suggesting that the SF1 polymorphism per se is not directly responsible for the loss of mc2r expression. Rather, ACTH resistance in this family of adrenocortical tumor cell mutants may be due to a closely linked gene on the SF1(S172) allele. Mouse strains with reportedly high steroidogenic capacity (C57Bl/6J, C57Bl/10J) also have the SF1(A172) allele while mouse strains with low steroidogenic capacity (C3H/HeJ, DBA/2J) have the SF1(S172) allele. These latter observations suggest that the two SF1 alleles also may be markers of steroidogenic potential among mouse strains.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Toronto, ON Canada M5G 1L6. bernard.schimmer@utoronto.ca
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Schimmer
authors.forename: Martha
authors.initials: M
authors.lastname: Cordova
authors.forename: Jennivine
authors.initials: J
authors.lastname: Tsao
authors.forename: Claudia
authors.initials: C
authors.lastname: Frigeri
mesh_terms: D000483:Alleles; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D005784:Gene Amplification; D018398:Homeodomain Proteins; D051379:Mice; D011110:Polymorphism, Genetic / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013256:Steroids / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013256:Steroids; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse