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

38 Citations (Scopus)

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 - 2002
Externally publishedYes

Fingerprint

Nuclear Receptor Coactivator 1
Haploinsufficiency
Thyroid Gland
Thyroid Hormones
Nuclear Receptor Coactivator 2
Thyroid Hormone Resistance Syndrome
Thyroid Hormone Receptors
Gene Dosage
Thyrotropin
Knockout Mice

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators : Evidence for haploinsufficiency. / Weiss, Roy E; Gehin, Martine; Jianming, X. U.; Sadow, Peter M.; O'Malley, Bert W.; Chambon, Pierre; Refetoff, Samuel.

In: Endocrinology, Vol. 143, No. 4, 2002, p. 1554-1557.

Research output: Contribution to journalArticle

Weiss, Roy E ; Gehin, Martine ; Jianming, X. U. ; Sadow, Peter M. ; O'Malley, Bert W. ; Chambon, Pierre ; Refetoff, Samuel. / Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators : Evidence for haploinsufficiency. In: Endocrinology. 2002 ; Vol. 143, No. 4. pp. 1554-1557.
@article{31c81f35911f48c4b7e2f50541f68840,
title = "Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: Evidence for haploinsufficiency",
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.",
author = "Weiss, {Roy E} and Martine Gehin and Jianming, {X. U.} and Sadow, {Peter M.} and O'Malley, {Bert W.} and Pierre Chambon and Samuel Refetoff",
year = "2002",
doi = "10.1210/en.143.4.1554",
language = "English (US)",
volume = "143",
pages = "1554--1557",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators

T2 - Evidence for haploinsufficiency

AU - Weiss, Roy E

AU - Gehin, Martine

AU - Jianming, X. U.

AU - Sadow, Peter M.

AU - O'Malley, Bert W.

AU - Chambon, Pierre

AU - Refetoff, Samuel

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036212356&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036212356&partnerID=8YFLogxK

U2 - 10.1210/en.143.4.1554

DO - 10.1210/en.143.4.1554

M3 - Article

C2 - 11897715

AN - SCOPUS:0036212356

VL - 143

SP - 1554

EP - 1557

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -