Abstract
The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TRα and TRβ loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TRα and TRβ genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TRβ receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TRβ, the products of the TRα gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TRβ, in contrast to TRα, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TRα and TRβ genes does not modify the maturation delay observed in TRα(-/-) mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TRα(-/-) animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 623-631 |
| Number of pages | 9 |
| Journal | EMBO Journal |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 1999 |
| Externally published | Yes |
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Keywords
- Bone
- Intestine
- Knockout
- Thyroid hormone receptor
- TSH
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Different functions for the thyroid hormone receptors TRα and TRβ in the control of thyroid hormone production and post-natal development. / Gauthier, Karine; Chassande, Olivier; Plateroti, Michela; Roux, Jean Paul; Legrand, Claude; Pain, Bertrand; Rousset, Bernard; Weiss, Roy E; Trouillas, Jacqueline; Samarut, Jacques.
In: EMBO Journal, Vol. 18, No. 3, 01.02.1999, p. 623-631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Different functions for the thyroid hormone receptors TRα and TRβ in the control of thyroid hormone production and post-natal development
AU - Gauthier, Karine
AU - Chassande, Olivier
AU - Plateroti, Michela
AU - Roux, Jean Paul
AU - Legrand, Claude
AU - Pain, Bertrand
AU - Rousset, Bernard
AU - Weiss, Roy E
AU - Trouillas, Jacqueline
AU - Samarut, Jacques
PY - 1999/2/1
Y1 - 1999/2/1
N2 - The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TRα and TRβ loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TRα and TRβ genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TRβ receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TRβ, the products of the TRα gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TRβ, in contrast to TRα, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TRα and TRβ genes does not modify the maturation delay observed in TRα(-/-) mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TRα(-/-) animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.
AB - The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TRα and TRβ loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TRα and TRβ genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TRβ receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TRβ, the products of the TRα gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TRβ, in contrast to TRα, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TRα and TRβ genes does not modify the maturation delay observed in TRα(-/-) mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TRα(-/-) animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.
KW - Bone
KW - Intestine
KW - Knockout
KW - Thyroid hormone receptor
KW - TSH
UR - http://www.scopus.com/inward/record.url?scp=0033081046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033081046&partnerID=8YFLogxK
U2 - 10.1093/emboj/18.3.623
DO - 10.1093/emboj/18.3.623
M3 - Article
C2 - 9927422
AN - SCOPUS:0033081046
VL - 18
SP - 623
EP - 631
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 3
ER -