Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: Evidence for haploinsufficiency

Roy E. Weiss, Martine Gehin, X. U. Jianming, Peter M. Sadow, Bert W. O'Malley, Pierre Chambon, Samuel Refetoff

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Steroid receptor coactivator (SRC) -1 and transcriptional intermediary factor (TIF) -2 are homologous nuclear receptor coactivators. We have investigated their possible redundancy as thyroid hormone (TH) coactivators by measuring thyroid function in compound SRC-1 and TIF-2 knock out (KO) mice. Whereas SRC-1 KO (SRC-1-/-) mice are resistant to TH and SRC-1+/- are not, we now demonstrate that TIF-2 KO (TIF-2-/-) mice have normal thyroid function. Yet double heterozygous, SRC-1+/-/TIF-2+/- mice manifested resistance to TH of a similar degree as that in mice completely deficient in SRC-1. KO of both SRC-1 and TIF-2 resulted in marked increases of serum TH and thyrotropin concentrations. This work demonstrates gene dosage effect in nuclear coactivators manifesting as haploinsufficiency and functional redundancy of SRC-1 and TIF-2.

Original languageEnglish (US)
Pages (from-to)1554-1557
Number of pages4
JournalEndocrinology
Volume143
Issue number4
DOIs
StatePublished - Apr 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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