Thyroid hormone receptor α1 mutants impair B lymphocyte development in a mouse model

Thyroid ◽  
2020 ◽  
Author(s):  
Sunmi Park ◽  
Xu-guang Zhu ◽  
Minjun Kim ◽  
Li Zhao ◽  
Sheue-yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Mouse Model ◽  
Hormone Receptor ◽  
B Lymphocyte ◽  
Thyroid Hormone Receptor ◽  
Lymphocyte Development ◽  
B Lymphocyte Development

scholarly journals Thyroid Hormone Receptor Alpha Mutations Lead to Epithelial Defects in the Adult Intestine in a Mouse Model of Resistance to Thyroid Hormone

Thyroid ◽  
2019 ◽  
Vol 29 (3) ◽  
pp. 439-448 ◽  
Author(s):  
Lingyu Bao ◽  
Julia Roediger ◽  
Sunmi Park ◽  
Liezhen Fu ◽  
Bingyin Shi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mouse Model ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Resistance To Thyroid Hormone ◽  
Receptor Alpha

scholarly journals Impaired Metabolic Effects of a Thyroid Hormone Receptor Beta-Selective Agonist in a Mouse Model of Diet-Induced Obesity

Thyroid ◽  
2010 ◽  
Vol 20 (5) ◽  
pp. 545-553 ◽  
Author(s):  
Melany Castillo ◽  
Beatriz C.G. Freitas ◽  
Matthew L. Rosene ◽  
Rafael A. Drigo ◽  
Renata Grozovsky ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mouse Model ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Metabolic Effects ◽  
Diet Induced Obesity ◽  
Selective Agonist ◽  
Receptor Beta

scholarly journals Role of TSH in the Spontaneous Development of Asymmetrical Thyroid Carcinoma in Mice with a Targeted Mutation in a Single Allele of the Thyroid Hormone-β Receptor

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 5090-5100 ◽  
Author(s):  
Li Zhao ◽  
Xuguang Zhu ◽  
Jeong Won Park ◽  
Laura Fozzatti ◽  
Mark Willingham ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Mouse Model ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Thyroid Tumor ◽  
Human Thyroid ◽  
Migration And Invasion ◽  
Wild Type ◽  
Single Allele

Abstract Mutations of the thyroid hormone receptor-β gene (THRB) cause resistance to thyroid hormone (RTH). A mouse model of RTH harboring a homozygous thyroid hormone receptor (TR)-β mutation known as PV (ThrbPV/PV mouse) spontaneously develops follicular thyroid cancer (FTC). Similar to RTH patients with mutations of two alleles of the THRB gene, the ThrbPV/PV mouse exhibits elevated thyroid hormones accompanied by highly nonsuppressible TSH. However, the heterozygous ThrbPV/+ mouse with mildly elevated TSH (∼2-fold) does not develop FTC. The present study examined whether the mutation of a single allele of the Thrb gene is sufficient to induce FTC in ThrbPV/+ mice under stimulation by high TSH. ThrbPV/+ mice and wild-type siblings were treated with propylthiouracil (PTU) to elevate serum TSH. ThrbPV/+mice treated with PTU (ThrbPV/+-PTU) spontaneously developed FTC similar to human thyroid cancer, but wild-type siblings treated with PTU did not. Interestingly, approximately 33% of ThrbPV/+-PTU mice developed asymmetrical thyroid tumors, as is frequently observed in human thyroid cancer. Molecular analyses showed activation of the cyclin 1-cyclin-dependent kinase-4-transcription factor E2F1 pathway to increase thyroid tumor cell proliferation of ThrbPV/+-PTU mice. Moreover, via extranuclear signaling, the PV also activated the integrin-Src-focal adhesion kinase-AKT-metalloproteinase pathway to increase migration and invasion of tumor cells. Therefore, mutation of a single allele of the Thrb gene is sufficient to drive the TSH-simulated hyperplastic thyroid follicular cells to undergo carcinogenesis. The present study suggests that the ThrbPV/+-PTU mouse model potentially could be used to gain insights into the molecular basis underlying the association between thyroid cancer and RTH seen in some affected patients.

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