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A Polymorphic Form of Steroidogenic Factor 1 Associated with ACTH Receptor Deficiency in Mouse Adrenal Cell Mutants
Author(s) -
SCHIMMER BERNARD P.,
CORDOVA MARTHA,
TSAO JENNIVINE,
FRIGERI CLAUDIA
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb03174.x
Subject(s) - steroidogenic factor 1 , biology , mutant , acth receptor , gene , nuclear receptor , mutation , receptor , allele , microbiology and biotechnology , genetics , adrenocorticotropic hormone , endocrinology , transcription factor , hormone
A bstract : We have described a family of adrenocortical tumor cell mutants (including clones OS3, Y6, and 10r9) that are resistant to ACTH because they fail to express the gene encoding the ACTH receptor (MC2R). The MC2R deficiency results from a mutation that impairs the activity of the nuclear receptor steroidogenic factor 1 (SF1) at the MC2R promoter. In this report, we show that ACTH resistance in the mutant clones is associated with a Sf1 gene that has Ser at codon 172 instead of Ala. In two of the three mutant clones, this Sf1 allele is amplified together with flanking DNA from chromosome 2 that includes the genes encoding germ cell nuclear factor and the beta‐type proteosome subunit Psmb7. SF1 A172 and SF1 S172 exhibit little or no difference in transcriptional activity in SF1‐dependent reporter gene assays, suggesting that SF1 S172 per se is not directly responsible for the loss of MC2R expression. Instead, the Sf1 S172 allele appears to be a marker of ACTH resistance in this family of adrenocortical tumor cell mutants, possibly reflecting the activity of a neighboring gene.