XB130 Deficiency Causes Congenital Hypothyroidism in Mice due to Disorganized Apical Membrane Structure and Function of Thyrocytes
| Autor: | Peter Arvan, Yun-Yan Xiang, Samuel Refetoff, Xiao Hui Liao, Yingchun Wang, Xiao-Hui Bai, Hae-Ra Cho, Hiroki Shimizu, Mingyao Liu, Junichi Sugihara, Hiroaki Toba, Sylvia L. Asa, Wei-Yang Lu |
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| Rok vydání: | 2021 |
| Předmět: |
Thyroid Hormones
endocrine system endocrine system diseases Endocrinology Diabetes and Metabolism macromolecular substances Mice Endocrinology Cell polarity Congenital Hypothyroidism medicine Animals Actin Adaptor Proteins Signal Transducing XB130 Chemistry Microfilament Proteins Thyroid Signal transducing adaptor protein Apical membrane medicine.disease Congenital hypothyroidism Cell biology Thyroxine medicine.anatomical_structure Thyroid Epithelial Cells Iodine Thyroid Dysfunction: Hypothyroidism Thyrotoxicosis and Thyroid Function Tests Hormone |
| Zdroj: | Thyroid |
| ISSN: | 1557-9077 1050-7256 |
| Popis: | Background: Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored. Methods: Xb130(−/−) mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction. Results: Xb130(−/−) mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of Xb130(−/−) mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal Xb130(−/−) mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina. Conclusion: XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism. |
| Databáze: | OpenAIRE |
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