Linked Life Data

8701076

Source:http://linkedlifedata.com/resource/pubmed/id/8701076

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-9-5
pubmed:abstractText
Thyroid hormone (T3) fulfills diverse functions in vertebrate development and physiology. These functions are thought to be mediated by two genes encoding the related T3 receptors. TR alpha and TR beta. The use of homologous recombination in embryonic stem cells to generate defined, single-gene mutations provides a powerful means to investigate the individual functions of TR alpha and TR beta in mice. We have shown that targeted inactivation of the TR beta gene results in goiter and elevated levels of thyroid hormone. Thyroid stimulating hormone (TSH), which is released by pituitary thyrotropes and is normally suppressed by increased levels of thyroid hormone, was present at elevated levels in homozygous mutant (Thrb-/-) mice. These findings suggest a unique role for TR beta that cannot be substituted by TR alpha in the T3-dependent feedback regulation of TSH transcription. Thrb-/- mice provide a recessive model for the human syndrome of resistance to thyroid hormone (RTH). Typically, RTH is associated with dominant mutations in TR beta. It is unknown whether TR alpha, TR beta, or other receptors are targets for inhibition in dominant RTH; however, the analysis of Thrb-/- mice suggests that antagonism of TR beta-mediated pathways underlies the disorder of the pituitary-thyroid axis. Thrb-/- mice also display defective maturation of auditory function, demonstrating that TR beta is essential for the development of hearing. Interestingly, hearing defects are generally absent in dominant RTH, indicating that in the auditory system, a dominant TR beta mutant cannot mimic the defect caused by loss of TR beta. This suggests the existence of tissue-specific mechanisms that modulate the activity of TR beta. These results define in vivo functions for TR beta and indicate that specificity in T3 signaling is conferred by distinct receptor genes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0079-9963
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Genetic analysis of thyroid hormone receptors in development and disease.
pubmed:affiliation
Mount Sinai School of Medicine, Department of Human Genetics, New York, New York 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't