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.
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Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis
Roepke, Torsten K; King, Elizabeth C; Reyna-Neyra, Andrea; Paroder, Monika; Purtell, Kerry; Koba, Wade; Fine, Eugene; Lerner, Daniel J; Carrasco, Nancy; Abbott, Geoffrey W
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, Volume 15 (10)
Nature Publishing Group (NPG) – Sep 20, 2009
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