A targeted dominant negative mutation of the thyroid hormone 1 receptor causes increased mortality, infertility, and dwarfism in mice
نویسندگان
چکیده
*Laboratory of Molecular Biology, National Cancer Institute, †Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; ‡Frederick Cancer Research and Development Facility, Frederick, MD 21702-1201; §Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037-1099; and ¶Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
منابع مشابه
A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice.
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)....
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Bone development is extremely sensitive to alterations in thyroid status. Recently, we analyzed the skeletal phenotypes of mice with the dominant negative resistance to thyroid hormone (RTH) mutation PV targeted to either the thyroid hormone receptor (TR) alpha1 or beta gene. This perspective summarizes our findings to date and explores the wider implications for thyroid status and T3 target ge...
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Genetic evidence from patients with mutations of the thyroid hormone receptor α gene (THRA) indicates that the dominant negative activity of mutants underlies the pathological manifestations. However, the molecular mechanisms by which TRα1 mutants exert dominant negative activity in vivo are not clear. We tested the hypothesis that the severe hypothyroidism in patients with THRA mutations is du...
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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...
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The growth-retarded (grt) mouse has an autosomal recessive hypothyroidism and the female shows lifelong infertility. We previously reported that these mutant phenotypes are caused by a deficiency in the enzymatic activity of tyrosylprotein sulfotransferase-2 (TPST2), and severe thyroid hypogenesis and consequent dwarfism are mainly due to the impairment of the tyrosine sulfation of thyroid-stim...
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تاریخ انتشار 2001