Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis

Torsten K. Roepke, Elizabeth C. King, Andrea Reyna-Neyra, Monika Paroder, Kerry Purtell, Wade Koba, Eugene Fine, Daniel J. Lerner, Nancy Carrasco, Geoffrey W. Abbott

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Thyroid dysfunction is a global health concern, causing defects including neurodevelopmental disorders, dwarfism and cardiac arrhythmia. Here, we show that the potassium channel subunits KCNQ1 and KCNE2 form a thyroid-stimulating hormone-stimulated, constitutively active, thyrocyte K+ channel required for normal thyroid hormone biosynthesis. Targeted disruption of Kcne2 in mice impaired thyroid iodide accumulation up to eightfold, impaired maternal milk ejection, halved milk tetraiodothyronine (T 4) content and halved litter size. Kcne2-deficient mice had hypothyroidism, dwarfism, alopecia, goiter and cardiac abnormalities including hypertrophy, fibrosis, and reduced fractional shortening. The alopecia, dwarfism and cardiac abnormalities were alleviated by triiodothyronine (T 3) and T 4 administration to pups, by supplementing dams with T 4 before and after they gave birth or by feeding the pups exclusively from Kcne2+/+ dams; conversely, these symptoms were elicited in Kcne2+/+ pups by feeding exclusively from Kcne2/ dams. These data provide a new potential therapeutic target for thyroid disorders and raise the possibility of an endocrine component to previously identified KCNE2-and KCNQ1-linked human cardiac arrhythmias.

Original languageEnglish (US)
Pages (from-to)1186-1194
Number of pages9
JournalNature Medicine
Volume15
Issue number10
DOIs
StatePublished - Sep 21 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., & Abbott, G. W. (2009). Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nature Medicine, 15(10), 1186-1194. https://doi.org/10.1038/nm.2029