Article (Scientific journals)
The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland.
van den Hove, Marie-France; Croizet-Berger, Karine; JOURET, François et al.
2006In Endocrinology, 147 (3), p. 1287-96
Peer Reviewed verified by ORBi
 

Files


Full Text
Endocrinology2006.pdf
Publisher postprint (390.87 kB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Animals; Anion Transport Proteins/biosynthesis/metabolism; Blotting, Western; Cell Membrane/metabolism; Chloride Channels/genetics/metabolism/physiology; DNA Primers/chemistry; Down-Regulation; Endocytosis; Endosomes/metabolism; Goiter/genetics/pathology; Iodides/metabolism; Iodine Radioisotopes/metabolism; Kidney/metabolism; Lysosomes/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Models, Statistical; RNA/metabolism; RNA, Messenger/metabolism; Subcellular Fractions/metabolism; Thyroglobulin/metabolism; Thyroid Gland/cytology/metabolism/pathology; Thyroid Hormones/metabolism; rab GTP-Binding Proteins/metabolism
Abstract :
[en] Genetic inactivation of ClC-5, a voltage-gated chloride channel prominently expressed in the kidney, leads to proteinuria because of defective apical endocytosis in proximal tubular cells. Because thyroid hormone secretion depends on apical endocytosis of thyroglobulin (Tg), we investigated whether ClC-5 is expressed in the thyroid and affects its function, using Clcn5-deficient knockout (KO) mice. We found that ClC-5 is highly expressed in wild-type mouse thyroid ( approximately 40% of mRNA kidney level). The protein was immunolocalized at the apical pole of thyrocytes. In Percoll gradients, ClC-5 overlapped with plasma membrane and early endosome markers, but best codistributed with the late endosomal marker, Rab7. ClC-5 KO mice were euthyroid (normal T4 and TSH serum levels) but developed a goiter with parallel iodine and Tg accumulation (i.e. normal Tg iodination level). When comparing ClC-5 KO with wild-type mice, thyroid 125I uptake after 1 h was doubled, incorporation into Tg was decreased by approximately 2-fold, so that trichloroacetic acid-soluble 125I increased approximately 4-fold. Enhanced 125I- efflux upon perchlorate and presence of 125I-Tg as autoradiographic rings at follicle periphery demonstrated delayed iodide organification. Endocytic trafficking of 125I-Tg toward lysosomes was not inhibited. Expression of pendrin, an I-/Cl- exchanger involved in apical iodide efflux, was selectively decreased by 60% in KO mice at mRNA and protein levels. Thus, ClC-5 is well expressed in the thyroid but is not critical for apical endocytosis, contrary to the kidney. Instead, the goiter associated with ClC-5 KO results from impaired rate of apical iodide efflux by down-regulation of pendrin expression.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
van den Hove, Marie-France
Croizet-Berger, Karine
JOURET, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
Guggino, Sandra E.
Guggino, William B.
Devuyst, Olivier
Courtoy, Pierre J.
Language :
English
Title :
The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland.
Publication date :
2006
Journal title :
Endocrinology
ISSN :
0013-7227
eISSN :
1945-7170
Publisher :
The Endocrine Society, United States - Maryland
Volume :
147
Issue :
3
Pages :
1287-96
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 21 November 2012

Statistics


Number of views
109 (0 by ULiège)
Number of downloads
159 (0 by ULiège)

Scopus citations®
 
74
Scopus citations®
without self-citations
70
OpenCitations
 
68

Bibliography


Similar publications



Contact ORBi