Source:http://linkedlifedata.com/resource/pubmed/id/11726557
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
23
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pubmed:dateCreated |
2001-11-29
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pubmed:abstractText |
Deletion of thyroid hormone receptor beta (TR beta), a ligand-dependent transcription factor encoded by the Thrb gene, causes deafness and thyroid hyperactivity in Thrb-null (Thrb(tm1/tm1)) mice and in a recessive form of the human syndrome of resistance to thyroid hormone. Here, we have determined that a targeted mutation (Thra(tm2)) in the related Thra gene, encoding thyroid hormone receptor alpha suppresses these phenotypes in mice. Thra encodes a TR alpha 1 receptor which is non-essential for hearing and a TR alpha 2 splice variant of unknown function that neither binds thyroid hormone nor transactivates. The Thra(tm2) mutation deletes TR alpha 2 and concomitantly causes overexpression of TR alpha 1 as a consequence of the exon structure of the gene. Thra(tm2/tm2) mice have normal auditory thresholds indicating that TR alpha 2 is dispensable for hearing, and have only marginally reduced thyroid activity. However, a potent function for the Thra(tm2) allele is revealed upon its introduction into Thrb(tm1/tm1) mice, where it suppresses the auditory and thyroid phenotypes caused by loss of TR beta. These findings reveal a novel modifying function for a Thra allele and suggest that increased expression of TR alpha 1 may substitute for the absence of TR beta. The TR isotypes generated by the distinct Thrb and Thra genes represent a small family of receptors that have diverged to mediate different physiological roles; however, the ability of changes in Thra expression to compensate for loss of Thrb indicates that many functions of these genes remain closely related.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Thyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin,
http://linkedlifedata.com/resource/pubmed/chemical/Thyroxine,
http://linkedlifedata.com/resource/pubmed/chemical/Triiodothyronine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0964-6906
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2701-8
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11726557-Animals,
pubmed-meshheading:11726557-Body Weight,
pubmed-meshheading:11726557-Cochlea,
pubmed-meshheading:11726557-DNA-Binding Proteins,
pubmed-meshheading:11726557-Deafness,
pubmed-meshheading:11726557-Evoked Potentials, Auditory, Brain Stem,
pubmed-meshheading:11726557-Gene Deletion,
pubmed-meshheading:11726557-Gene Expression,
pubmed-meshheading:11726557-Genotype,
pubmed-meshheading:11726557-Hair Cells, Auditory, Inner,
pubmed-meshheading:11726557-Membrane Potentials,
pubmed-meshheading:11726557-Mice,
pubmed-meshheading:11726557-Mice, Inbred BALB C,
pubmed-meshheading:11726557-Mice, Inbred C57BL,
pubmed-meshheading:11726557-Mice, Inbred Strains,
pubmed-meshheading:11726557-Mice, Mutant Strains,
pubmed-meshheading:11726557-Mutation,
pubmed-meshheading:11726557-Potassium Channels,
pubmed-meshheading:11726557-RNA, Messenger,
pubmed-meshheading:11726557-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:11726557-Receptors, Thyroid Hormone,
pubmed-meshheading:11726557-Suppression, Genetic,
pubmed-meshheading:11726557-Thyroid Gland,
pubmed-meshheading:11726557-Thyrotropin,
pubmed-meshheading:11726557-Thyroxine,
pubmed-meshheading:11726557-Triiodothyronine
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pubmed:year |
2001
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pubmed:articleTitle |
Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene.
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pubmed:affiliation |
Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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