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...

Descripción completa

Detalles Bibliográficos
Autor: Maldonado Barragán, Ana Margarita
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
id ES_9698384c07770ccac3ef1fc0478f1353
oai_identifier_str oai:www.tdx.cat:10803/671367
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Deciphering the role of RBM10 in development and cancer using a genetic mouse model
title Deciphering the role of RBM10 in development and cancer using a genetic mouse model
spellingShingle Deciphering the role of RBM10 in development and cancer using a genetic mouse model
Maldonado Barragán, Ana Margarita
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
title_short Deciphering the role of RBM10 in development and cancer using a genetic mouse model
title_full Deciphering the role of RBM10 in development and cancer using a genetic mouse model
title_fullStr Deciphering the role of RBM10 in development and cancer using a genetic mouse model
title_full_unstemmed Deciphering the role of RBM10 in development and cancer using a genetic mouse model
title_sort Deciphering the role of RBM10 in development and cancer using a genetic mouse model
dc.creator.none.fl_str_mv Maldonado Barragán, Ana Margarita
author Maldonado Barragán, Ana Margarita
author_facet Maldonado Barragán, Ana Margarita
author_role author
dc.contributor.none.fl_str_mv Marqués, Miriam
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
dc.subject.none.fl_str_mv 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
topic 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
description 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
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/671367
url http://hdl.handle.net/10803/671367
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 196 p.
application/pdf
application/pdf
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413962928357376
spelling Deciphering the role of RBM10 in development and cancer using a genetic mouse modelMaldonado Barragán, Ana MargaritaRBM10 Alternative splicing Development Bladder cancer Organoids RBM10 Splicing alternativo Desarrollo Cáncer de Vejiga OrganoidesRBM10Alternative splicingDevelopmentBladder cancerOrganoidsSplicing alternativoDesarrolloCáncer de VejigaOrganoides616.6Short 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 progressionPara revelar cómo la pérdida de RBM10 contribuye al desarrollo embrionario y al cáncer, hemos establecido modelos de ratón Rbm10 knockout condicionales y constitutivos, y hemos analizado sus fenotipos a nivel celular y de organismo. La inactivación constitutiva de Rbm10 en la línea germinal resulta en letalidad embrionaria en machos y parcialmente recapitula las malformaciones asociadas al síndrome TARP. La inactivación de Rbm10 ubicua en ratones jóvenes es bien tolerada, indicando que la proteína es dispensable en la etapa adulta. En organoides uroteliales normales, la inactivación de Rbm10 in vitro genera independencia parcial de EGF y un fenotipo luminal con características de epitelio estratificado. Asimismo, el análisis de los tumores humanos reveló que la inactivación de RBM10 es una alteración genética temprana en la carcinogénesis de vejiga. Finalmente, he generado numerosas herramientas para continuar analizando los mecanismos moleculares a través de los cuales la pérdida de función de RBM10 contribuye al cáncer de vejiga. Estos resultados validan nuestros modelos para el estudio del síndrome de TARP y de cáncer de vejiga, permitiendo la identificación de dianas de splicing y mecanismos moleculares mediados por RBM10 relevantes para la progresión de la enfermedad.Programa de doctorat en BiomedicinaMarqués, MiriamUniversitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut202120212021info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion196 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/671367TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6713672026-06-14T12:46:07Z
score 15,300724

Similares en LA Referencia