NDLI: Mice with a targeted mutation in the thyroid hormone β receptor gene exhibit impaired growth and resistance to thyroid hormone

Content Provider	PubMed Central
Author	Masahiro, Kaneshige Kaneshige, Kumiko Zhu, Xu-guang Dace, Alexandra Garrett, Lisa Carter, Todd A. Rasa, Kazlauskaite Pankratz, Daniel G. Anthony, Wynshaw-boris Samuel, Refetoff Weintraub, Bruce Willingham, Mark C. Barlow, Carrolee Cheng, Sheue-yann
Copyright Year	2000
Abstract	Patients with mutations in the thyroid hormone receptor β (TRβ) 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 TRβ in vivo, we generated mice with a targeted mutation in the TRβ gene (TRβ 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 TRβ gene. Importantly, we identified abnormal expression patterns of several genes in tissues of TRβ 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 TRβ 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.
Related Links	http://dx.doi.org/10.1073/pnas.230285997
Ending Page	13214
Page Count	6
Starting Page	13209
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-11-21
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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