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

Endocrinology. 2002 Apr;143(4):1554-7. doi: 10.1210/endo.143.4.8828.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Gene Dosage
  • Haplotypes / genetics
  • Heterozygote
  • Histone Acetyltransferases
  • Homozygote
  • Male
  • Mice
  • Mice, Knockout
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2
  • Thyroid Function Tests
  • Thyroid Gland / physiology*
  • Thyroid Hormones / physiology
  • Thyrotropin / blood
  • Thyroxine / blood
  • Thyroxine / physiology
  • Transcription Factors / genetics*
  • Triiodothyronine / blood
  • Triiodothyronine / physiology


  • Ncoa2 protein, mouse
  • Nuclear Receptor Coactivator 2
  • Thyroid Hormones
  • Transcription Factors
  • Triiodothyronine
  • Thyrotropin
  • Histone Acetyltransferases
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1
  • Thyroxine