Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction

Xu Guang Zhu, Masahiro Kaneshige, Albert F. Parlow, Evan Chen, Rosemarie D. Hunziker, Michael Mcdonald, Sheue Yann Cheng

Research output: Contribution to journalArticle

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Abstract

Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of the thyroid hormone receptor β gene (TRβ). One of the symptoms in some affected individuals is growth retardation. To understand the molecular basis of growth retardation in these patients with RTH, a transgenic mouse was prepared in which the expression of the TRβ1 mutant PV was targeted to the pituitary using the promoter of the glycoprotein hormone α-subunit. The PV mutant was originally identified in a patient with severe growth impairment. The PV mutation is a C-insertion at codon 448 of the TRβ gene and leads to a frame-shift of the carboxyl-terminal 14 amino acids of TRβ1, resulting in total loss of triiodothyronine (T3) binding and transcriptional activation. PV was selectively expressed in the pituitary of the transgenic mouse and not in other tissues examined. The transgenic mice showed a significant impairment in weight gain. However, no changes in the serum level of thyroid-stimulating hormone were seen, and no elevation of thyroid hormones was detected in the transgenic mice. The circulating levels of growth hormone and insulin-like growth factor I were not affected in the transgenic mice, suggesting that the growth impairment in RTH is complex and is mediated by pathways that are yet to be elucidated.

Original languageEnglish (US)
Pages (from-to)1137-1145
Number of pages9
JournalThyroid
Volume9
Issue number11
DOIs
StatePublished - Jan 1 1999

Fingerprint

Thyroid Hormone Receptors
Transgenic Mice
Thyroid Hormone Resistance Syndrome
Weight Loss
Growth
Mutation
Inborn Genetic Diseases
Triiodothyronine
Thyrotropin
Insulin-Like Growth Factor I
Thyroid Hormones
Codon
Transcriptional Activation
Growth Hormone
Genes
Weight Gain
Glycoproteins
Hormones
Amino Acids
Serum

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction. / Zhu, Xu Guang; Kaneshige, Masahiro; Parlow, Albert F.; Chen, Evan; Hunziker, Rosemarie D.; Mcdonald, Michael; Cheng, Sheue Yann.

In: Thyroid, Vol. 9, No. 11, 01.01.1999, p. 1137-1145.

Research output: Contribution to journalArticle

Zhu, Xu Guang ; Kaneshige, Masahiro ; Parlow, Albert F. ; Chen, Evan ; Hunziker, Rosemarie D. ; Mcdonald, Michael ; Cheng, Sheue Yann. / Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction. In: Thyroid. 1999 ; Vol. 9, No. 11. pp. 1137-1145.
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