Deciphering the role of RBM10 in development and cancer using a genetic mouse model
Short explanation English To reveal how RBM10 loss contributes to development and cancer we have established Rbm10 constitutive and conditional knockout mouse models and have analyzed phenotypes at the organismal and cellular level. Constitutive inactivation of Rbm10 in the mouse germline results in...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/671367 |
| Acceso en línea: | http://hdl.handle.net/10803/671367 |
| Access Level: | acceso abierto |
| Palabra clave: | RBM10 Alternative splicing Development Bladder cancer Organoids RBM10 Splicing alternativo Desarrollo Cáncer de Vejiga Organoides RBM10 Alternative splicing Development Bladder cancer Organoids Splicing alternativo Desarrollo Cáncer de Vejiga Organoides 616.6 |
| Sumario: | Short explanation English To reveal how RBM10 loss contributes to development and cancer we have established Rbm10 constitutive and conditional knockout mouse models and have analyzed phenotypes at the organismal and cellular level. Constitutive inactivation of Rbm10 in the mouse germline results in partial male embryonic lethality and partially recapitulates TARP syndrome. Tissue-wide Rbm10 inactivation in young mice is well tolerated, indicating that the protein is dispensable in adulthood. In normal urothelial organoids, Rbm10 inactivation in vitro leads to partial EGF-independence and a luminal-like phenotype with stratified epithelium features. Further, our analysis on human tumors reveals that RBM10 inactivation is an early genetic alteration in bladder carcinogenesis. I have also generated several tools to further analyze the molecular mechanisms through which RBM10 loss-of-function contributes to bladder cancer. Altogether, the results validate the newly developed strain as a valuable model to study TARP syndrome and urothelial cancer, allowing the identification of RBM10-related splicing targets and molecular mechanisms relevant to disease progression |
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