ArticleEndocrinology2014
Thyroid hormone receptor α mutation causes a severe and thyroxine-resistant skeletal dysplasia in female mice.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility.Scientific reports · 2025Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Long-term follow-up results and treatment outcomes of children and adults with resistance to thyroid hormone alpha.Journal of endocrinological investigation · 2023Article
- Morphological and Functional Colonic Defects Caused by a Mutated Thyroid Hormone Receptor α.Thyroid : official journal of the American Thyroid Association · 2023Article
- Sfrp4 expression in thyroxine treated calvarial cells.Life sciences · 2022Article
- Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects.Stem cell research & therapy · 2021Article
- Thyroid Hormone Receptor α Regulates Autophagy, Mitochondrial Biogenesis, and Fatty Acid Use in Skeletal Muscle.Endocrinology · 2021Article
- The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and AdultsJournal of clinical research in pediatric endocrinology · 2021Review
- Article
- Role of thyroid hormones in craniofacial development.Nature reviews. Endocrinology · 2020Review
- Generation of Novel Genetic Models to Dissect Resistance to Thyroid Hormone Receptor α in Zebrafish.Thyroid : official journal of the American Thyroid Association · 2020Article
- Genetic and Pharmacological Targeting of Transcriptional Repression in Resistance to Thyroid Hormone Alpha.Thyroid : official journal of the American Thyroid Association · 2019Article
- Thyroid Hormone Receptor Alpha Mutations Lead to Epithelial Defects in the Adult Intestine in a Mouse Model of Resistance to Thyroid Hormone.Thyroid : official journal of the American Thyroid Association · 2019Article
- Thyroid Hormone Signaling in the Development of the Endochondral Skeleton.Vitamins and hormones · 2018Review
- Thyroid diseases and bone health.Journal of endocrinological investigation · 2018Review
- Noncanonical thyroid hormone signaling mediates cardiometabolic effects in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- NCOR1 modulates erythroid disorders caused by mutations of thyroid hormone receptor α1.Scientific reports · 2017Article
- Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α.Endocrine connections · 2017Article
- Defective erythropoiesis caused by mutations of the thyroid hormone receptor α gene.PLoS genetics · 2017Article
- An Essential Physiological Role for MCT8 in Bone in Male Mice.Endocrinology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1(PV/+) mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1(PV/+) mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1(PV/+) mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.