文章基本信息

标题：Mice with a targeted mutation in the thyroid hormone β receptor gene exhibit impaired growth and resistance to thyroid hormone
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作者：Masahiro Kaneshige ; Kumiko Kaneshige ; Xu-guang Zhu 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：24
页码：13209-13214
DOI：10.1073/pnas.230285997
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Patients with mutations in the thyroid hormone receptor {beta} (TR{beta}) gene manifest resistance to thyroid hormone (RTH), resulting in a constellation of variable phenotypic abnormalities. To understand the molecular basis underlying the action of mutant TR{beta} in vivo, we generated mice with a targeted mutation in the TR{beta} gene (TR{beta}PV; PV, mutant thyroid hormone receptor kindred PV) by using homologous recombination and the Cre/loxP system. Mice expressing a single PVallele showed the typical abnormalities of thyroid function found in heterozygous humans with RTH. Homozygous PV mice exhibit severe dysfunction of the pituitary-thyroid axis, impaired weight gains, and abnormal bone development. This phenotype is distinct from that seen in mice with a null mutation in the TR{beta} gene. Importantly, we identified abnormal expression patterns of several genes in tissues of TR{beta}PV mice, demonstrating the interference of the mutant TR with the gene regulatory functions of the wild-type TR in vivo. These results show that the actions of mutant and wild-type TR{beta} in vivo are distinct. This model allows further study of the molecular action of mutant TR in vivo, which could lead to better treatment for RTH patients.