Potassium channel subunits: diagnostic & therapeutic targets for thyroid disease
- *Abstract
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Inventions:
- A method to treat hyperthyroid disease by administering a compound known to block the activity of KCNQ1 or KCNE2 or that blocks the KCNQ1-KCNE2 channel.
- A method to treat hypothyroid disease by administering a compound known to promote the activity of KCNQ1 or KCNE2 or that opens the KCNQ1-KCNE2 channel.
- A method to diagnose thyroid disease or determine a susceptibility to developing thyroid disease comprising measuring a patient sample to identify a mutation in KCNQ1 or KCNE2
Thyroid dysfunction is a global health concern, causing defects including neurodevelopmental disorders, dwarfism and cardiac arrhythmia. Investigators at Cornell have shown that 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 exclusively from Kcne2+/+ dams; conversely, these symptoms were elicited in Kcne2+/+ pups by feeding exclusively from Kcne2 -/- dams.
These data provide a new therapeutic and diagnostic target for thyroid disorders and raise the possibility of an endocrine component to previously identified KCNE2- and KCNQ1-linked human cardiac arrhythmias.
- *Licensing
- BrianJ. Kellybjk44@cornell.edu212-746-6186
- 其他
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(2009) Roepke TK et al. Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nat Med 15(10):1186-94.
- 國家/地區
- 美國
