ArticleProceedings of the National Academy of Sciences of the United States of America2001
A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 190 citations in OpenAlex.
- Intrafamilial and Age-Dependent Variability in Resistance to Thyroid Hormone Alpha: A Case Report.Hormone research in paediatrics · 2026Article
- TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility.Scientific reports · 2025Article
- Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells.Cancer cell · 2024Article
- Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage.Reproductive biology and endocrinology : RB&E · 2023Article
- Morphological and Functional Colonic Defects Caused by a Mutated Thyroid Hormone Receptor α.Thyroid : official journal of the American Thyroid Association · 2023Article
- Structure-Guided Approach to Relieving Transcriptional Repression in Resistance to Thyroid Hormone α.Molecular and cellular biology · 2022Article
- Thyroid Hormone Receptor α Regulates Autophagy, Mitochondrial Biogenesis, and Fatty Acid Use in Skeletal Muscle.Endocrinology · 2021Article
- Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk.JCI insight · 2021Article
- Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior.International journal of molecular sciences · 2021Article
- Effect of Thyromimetic GC-1 Selective Signaling on Reproductive and Lactational Performance in the Hypothyroid Rat.European thyroid journal · 2021Article
- Thyroid Hormone Receptor α1 Mutants Impair B Lymphocyte Development in a Mouse Model.Thyroid : official journal of the American Thyroid Association · 2021Article
- Thyroid hormone: sex-dependent role in nervous system regulation and disease.Biology of sex differences · 2021Review
- The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and AdultsJournal of clinical research in pediatric endocrinology · 2021Review
- Persistent COUP-TFII expression underlies the myopathy and impaired muscle regeneration observed in resistance to thyroid hormone-alpha.Scientific reports · 2021Article
- DUSP5 expression in left ventricular cardiomyocytes of young hearts regulates thyroid hormone (T3)-induced proliferative ERK1/2 signaling.Scientific reports · 2020Article
- Akt isoform-specific effects on thyroid cancer development and progression in a murine thyroid cancer model.Scientific reports · 2020Article
- A Direct Comparison of Thyroid Hormone Receptor Protein Levels in Mice Provides Unexpected Insights into Thyroid Hormone Action.Thyroid : official journal of the American Thyroid Association · 2020Article
- A Pivotal Genetic Program Controlled by Thyroid Hormone during the Maturation of GABAergic Neurons.iScience · 2020Article
- 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
15 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the thyroid hormone receptor beta (TRbeta) gene result in resistance to thyroid hormone. However, it is unknown whether mutations in the TRalpha gene could lead to a similar disease. To address this question, we prepared mutant mice by targeting mutant thyroid hormone receptor kindred PV (PV) mutation to the TRalpha gene locus by means of homologous recombination (TRalpha1PV mice). The PV mutation was derived from a patient with severe resistance to thyroid hormone that has a frameshift of the C-terminal 14 aa of TRbeta1. We knocked in the same PV mutation to the corresponding TRalpha gene locus to compare the phenotypes of TRalpha1(PV/+) mice with those of TRbeta(PV/+) mice. TRalpha1(PV/+) mice were viable, indicating that the mutation of the TRalpha gene is not embryonic lethal. In drastic contrast to the TRbeta(PV/+) mice, which do not exhibit a growth abnormality, TRalpha1(PV/+) mice were dwarfs. These dwarfs exhibited increased mortality and reduced fertility. In contrast to TRbeta(PV/+) mice, which have a hyperactive thyroid, TRalpha1(PV/+) mice exhibited mild thyroid failure. The in vivo pattern of abnormal regulation of T3 target genes in TRalpha1(PV/+) mice was unique from those of TRbeta(PV/+) mice. The distinct phenotypes exhibited by TRalpha1(PV/+) and TRbeta(PV/+) mice indicate that the in vivo functions of TR mutants are isoform-dependent. The TRalpha1(PV/+) mice may be used as a tool to uncover human diseases associated with mutations in the TRalpha gene and, furthermore, to understand the molecular mechanisms by which TR isoforms exert their biological activities.
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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.