Use of mouse models to establish genotype-phenotype correlations in Williams-Beuren syndrome
Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the common deletion of 26-28 contiguous genes in the 7q11.23 region, which poses difficulties to the establishment of genotype-phenotype correlations. The use of mouse models would broader the knowledge of the syndrome, the ro...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/101408 |
| Acceso en línea: | http://hdl.handle.net/10803/101408 |
| Access Level: | acceso abierto |
| Palabra clave: | Williams-Beuren syndrome Mouse models Transcriptome profile Pathway enrichment Binding motif Cardiovascular phenotype General transcription factor II-I (Gtf2i) Neutrophil cytosolic factor 1 (Ncf1) Síndrome de Williams-Beuren Models de ratolí Perfil transcriptòmic Enriquiment de vies moleculars Motiu d’unió Fenotip cardiovascular 575 |
| Sumario: | Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the common deletion of 26-28 contiguous genes in the 7q11.23 region, which poses difficulties to the establishment of genotype-phenotype correlations. The use of mouse models would broader the knowledge of the syndrome, the role of deleted genes, affected pathways and possible treatments. In this thesis project, several mouse models, tissues and cells have been used to define the phenotypes at different levels, the deregulated genes and pathways and to discover modifying elements and novel treatments for the cardiovascular phenotype. In addition, a new binding motif has been described for Gtf2i, a deleted gene encoding a transcription factor with a major role in WB, providing new target genes from deregulated pathways. The obtained results reveal the essential role of mouse models for the study of Williams-Beuren syndrome and provide new treatments options and affected pathways and genes which could be future treatment targets. |
|---|