期刊
NATURE MEDICINE
卷 15, 期 10, 页码 1186-U117出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2029
关键词
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资金
- US National Heart, Lung, and Blood Institute [HL079275]
- American Heart Association [0855756D]
- US National Institute of Diabetes and Digestive and Kidney Diseases [DK41544]
- US National Cancer Institute [CA098390]
- US National Institutes of Health [5T32GM002788]
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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