An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice

Abstract The sodium/iodide symporter (NIS) mediates active iodide (I−) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I− transport defect (ITD...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Giuseppe Ferrandino, Rachel R. Kaspari, Andrea Reyna-Neyra, Nabil E. Boutagy, Albert J. Sinusas, Nancy Carrasco
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/adfd886097eb46a7ac67c7f88e8b5af1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:adfd886097eb46a7ac67c7f88e8b5af1
record_format	dspace
spelling	oai:doaj.org-article:adfd886097eb46a7ac67c7f88e8b5af12021-12-02T15:06:13ZAn extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice10.1038/s41598-017-04326-z2045-2322https://doaj.org/article/adfd886097eb46a7ac67c7f88e8b5af12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04326-zhttps://doaj.org/toc/2045-2322Abstract The sodium/iodide symporter (NIS) mediates active iodide (I−) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I− transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I−. Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate (99mTcO4 −). NIS KO mice showed undetectable serum T4 and very low serum T3 levels when fed a diet supplying the minimum I− requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I− diet partially rescued TH biosynthesis, demonstrating that, at high I− concentrations, I− enters the thyroid through routes other than NIS.Giuseppe FerrandinoRachel R. KaspariAndrea Reyna-NeyraNabil E. BoutagyAlbert J. SinusasNancy CarrascoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giuseppe Ferrandino Rachel R. Kaspari Andrea Reyna-Neyra Nabil E. Boutagy Albert J. Sinusas Nancy Carrasco An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
description	Abstract The sodium/iodide symporter (NIS) mediates active iodide (I−) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I− transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I−. Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate (99mTcO4 −). NIS KO mice showed undetectable serum T4 and very low serum T3 levels when fed a diet supplying the minimum I− requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I− diet partially rescued TH biosynthesis, demonstrating that, at high I− concentrations, I− enters the thyroid through routes other than NIS.
format	article
author	Giuseppe Ferrandino Rachel R. Kaspari Andrea Reyna-Neyra Nabil E. Boutagy Albert J. Sinusas Nancy Carrasco
author_facet	Giuseppe Ferrandino Rachel R. Kaspari Andrea Reyna-Neyra Nabil E. Boutagy Albert J. Sinusas Nancy Carrasco
author_sort	Giuseppe Ferrandino
title	An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
title_short	An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
title_full	An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
title_fullStr	An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
title_full_unstemmed	An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice
title_sort	extremely high dietary iodide supply forestalls severe hypothyroidism in na+/i− symporter (nis) knockout mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/adfd886097eb46a7ac67c7f88e8b5af1
work_keys_str_mv	AT giuseppeferrandino anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT rachelrkaspari anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT andreareynaneyra anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT nabileboutagy anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT albertjsinusas anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT nancycarrasco anextremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT giuseppeferrandino extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT rachelrkaspari extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT andreareynaneyra extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT nabileboutagy extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT albertjsinusas extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice AT nancycarrasco extremelyhighdietaryiodidesupplyforestallsseverehypothyroidisminnaisymporternisknockoutmice
_version_	1718388536781045760

An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I− symporter (NIS) knockout mice

Ejemplares similares