Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine
Author | dc.contributor.author | Jansen, Jurgen | es_CL |
Author | dc.contributor.author | Friesema, Edith C. H. | es_CL |
Author | dc.contributor.author | Kester, Monique H. A. | es_CL |
Author | dc.contributor.author | Milici, Carmelina | es_CL |
Author | dc.contributor.author | Reeser, Maarten | es_CL |
Author | dc.contributor.author | Grüeters, Annette | es_CL |
Author | dc.contributor.author | Barrett, Timothy G. | es_CL |
Author | dc.contributor.author | Mancilla Vergara, Edna | es_CL |
Author | dc.contributor.author | Svensson, Johan | es_CL |
Author | dc.contributor.author | Wemeau, Jean-Louis | es_CL |
Author | dc.contributor.author | Busi da Silva Canalli, Maria Heloisa | es_CL |
Author | dc.contributor.author | Lundgren, Johan | es_CL |
Author | dc.contributor.author | McEntagart, Meriel E. | es_CL |
Author | dc.contributor.author | Hopper, Neil | es_CL |
Author | dc.contributor.author | Arts, Willem Frans | es_CL |
Author | dc.contributor.author | Visser, Theo J. | es_CL |
Admission date | dc.date.accessioned | 2008-05-14T13:54:36Z | |
Available date | dc.date.available | 2008-05-14T13:54:36Z | |
Publication date | dc.date.issued | 2007 | es_CL |
Cita de ítem | dc.identifier.citation | JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM Vol. 92 JUN 2007 6 2378-2381 | es_CL |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/127460 | |
General note | dc.description | Publicación ISI | es_CL |
Abstract | dc.description.abstract | Context: T-3 action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T-3 uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T-3 levels. Objective: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T-3. Design: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T-3 uptake, 2) T-3 metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry. Results: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8. Conclusion: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T-3 levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T-3 in central neurons. | es_CL |
Lenguage | dc.language.iso | en | es_CL |
Keywords | dc.subject | THYROID-HORMONE TRANSPORTER | es_CL |
Area Temática | dc.subject.other | Endocrinology & Metabolism | es_CL |
Título | dc.title | Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine | es_CL |
Document type | dc.type | Artículo de revista |
Files in this item
This item appears in the following Collection(s)
-
Artículos de revistas
Artículos de revistas