Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis Export

@article{citeulike:5915777, 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 (T4) 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 (T3) and T4 administration to pups, by supplementing dams with T4 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.}, author = {Roepke, Torsten K. and King, Elizabeth C. and Reyna-Neyra, Andrea and Paroder, Monika and Purtell, Kerry and Koba, Wade and Fine, Eugene and Lerner, Daniel J. and Carrasco, Nancy and Abbott, Geoffrey W.}, citeulike-article-id = {5915777}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nm.2029}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nm.2029}, day = {20}, doi = {10.1038/nm.2029}, issn = {1078-8956}, journal = {Nature Medicine}, keywords = {metabolism}, month = {September}, number = {10}, pages = {1186--1194}, posted-at = {2009-10-14 00:39:46}, priority = {2}, publisher = {Nature Publishing Group}, title = {Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis}, url = {http://dx.doi.org/10.1038/nm.2029}, volume = {15}, year = {2009} }

TY - JOUR ID - citeulike:5915777 L3 - citeulike-article-id:5915777 N2 - 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 (T4) 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 (T3) and T4 administration to pups, by supplementing dams with T4 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. IS - 10 JF - Nature Medicine SN - 1078-8956 EP - 1194 TI - Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis PB - Nature Publishing Group VL - 15 SP - 1186 KW - metabolism AU - Roepke, Torsten AU - King, Elizabeth AU - Reyna-Neyra, Andrea AU - Paroder, Monika AU - Purtell, Kerry AU - Koba, Wade AU - Fine, Eugene AU - Lerner, Daniel AU - Carrasco, Nancy AU - Abbott, Geoffrey PY - 2009/09/20/ UR - http://dx.doi.org/10.1038/nm.2029 ER -