Thyroid Hormone Receptor Alpha Mutations Lead to Epithelial Defects in the Adult Intestine in a Mouse Model of Resistance to Thyroid Hormone.
adult organ-specific stem cell
cell proliferation and differentiation
resistance to thyroid hormone
small intestine
thyroid hormone receptor
Journal
Thyroid : official journal of the American Thyroid Association
ISSN: 1557-9077
Titre abrégé: Thyroid
Pays: United States
ID NLM: 9104317
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
pubmed:
1
1
2019
medline:
25
2
2020
entrez:
1
1
2019
Statut:
ppublish
Résumé
The thyroid hormone triiodothyronine (T3) is critical for vertebrate development and affects the function of many adult tissues and organs. Its genomic effects are mediated by thyroid hormone nuclear receptors (TRs) present in all vertebrates. The discovery of patients with resistance to thyroid hormone (RTHβ) >50 years ago and subsequent identification of genetic mutations in only the THRB gene in these patients suggest that mutations in the THRA gene may have different pathological manifestations in humans. Indeed, the recent discovery of a number of human patients carrying heterozygous mutations in the THRA gene (RTHα) revealed a distinct phenotype that was not observed in RTH patients with THRB gene mutations (RTHβ). That is, RTHα patients have constipation, implicating intestinal defects caused by THRA gene mutations. To determine how TRα1 mutations affect the intestine, this study analyzed a mutant mouse expressing a strong dominantly negative TRα1 mutant (denoted TRα1PV; Thra1 In adult Thra1 The findings suggest that further analysis of this mouse model should help to reveal the molecular and physiological defects in the intestine caused by TRα mutations and to determine the underlying mechanisms.
Sections du résumé
BACKGROUND
The thyroid hormone triiodothyronine (T3) is critical for vertebrate development and affects the function of many adult tissues and organs. Its genomic effects are mediated by thyroid hormone nuclear receptors (TRs) present in all vertebrates. The discovery of patients with resistance to thyroid hormone (RTHβ) >50 years ago and subsequent identification of genetic mutations in only the THRB gene in these patients suggest that mutations in the THRA gene may have different pathological manifestations in humans. Indeed, the recent discovery of a number of human patients carrying heterozygous mutations in the THRA gene (RTHα) revealed a distinct phenotype that was not observed in RTH patients with THRB gene mutations (RTHβ). That is, RTHα patients have constipation, implicating intestinal defects caused by THRA gene mutations.
METHODS
To determine how TRα1 mutations affect the intestine, this study analyzed a mutant mouse expressing a strong dominantly negative TRα1 mutant (denoted TRα1PV; Thra1
RESULTS
In adult Thra1
CONCLUSIONS
The findings suggest that further analysis of this mouse model should help to reveal the molecular and physiological defects in the intestine caused by TRα mutations and to determine the underlying mechanisms.
Identifiants
pubmed: 30595106
doi: 10.1089/thy.2018.0340
pmc: PMC6437623
doi:
Substances chimiques
Receptors, Thyroid Hormone
0
Thyroid Hormone Receptors alpha
0
Triiodothyronine
06LU7C9H1V
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
439-448Références
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