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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2001-11-29
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2701-8
pubmed:dateRevised
2007-11-15
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
pubmed:year
2001
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.
pubmed:affiliation
Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't