The role of microRNAs in X-linked myotubular myopathy

Detalhes bibliográficos
Autor(a) principal: Fontes, Mariana Miranda
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/1471
Resumo: Tese de mestrado, Biologia (Bioplogia Humana e Ambiente), 2009, Universidade de Lisboa, Faculdade de Ciências
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spelling The role of microRNAs in X-linked myotubular myopathyBiologia molecularMiopatia miotubularTeses de mestradoTese de mestrado, Biologia (Bioplogia Humana e Ambiente), 2009, Universidade de Lisboa, Faculdade de CiênciasX-linked myotubular myopathy (XLMTM) is a congenital neuromuscular disorder characterized by profound hypotonia and severe skeletal muscle weakness in the affected newborn males. The pathology is associated with mutations in the MTM1 gene leading to loss of function of the resulting encoded protein, myotubularin. Myotubularin is a phosphoinositol lipid phosphases known to be involved in endosome trafficking and membrane remodeling, however, the molecular mechanisms underlying myotubular myopathy are not yet clear. MicroRNAs (miRNAs) are post transcriptional modulators of gene expression and play an important role in many developmental processes and diseases. To identify functional miRNA-protein networks that may be dysregulated in myotubular myopathy, we performed miRNA as well as mRNA expression profiling of skeletal muscle of Mtm1 knockout mice. Bioinformatic analysis and real-time RTPCR validation resulted in identification of 12 miRNAs that showed significantly differential expression in Mtm1 mice. The functional targets of these miRNAs in myotubular myopathy were identified by a combinatorial approach in which computationally predicted targets genes of these 12 miRNAs were matched with statistically altered genes obtained by mRNA profiling of skeletal muscle tissues from Mtm1 mice. Ontological classification of target genes revealed genes primarily belonging to skeletal muscle development and maintenance, regulation of cell cycle and differentiation of muscle fibers. Expression analyses of miRNA-target genes identified from this study were also performed during earlier developmental time points (2 and 4 weeks) in Mtm1 mice for a better comprehensive insight of miRNA-mRNAs in the progression of the disease. We observed that an increase in the severity of XLMTM is associated with an increase in the fold change of several miRNAs and their target genes, suggesting their crucial role in pathology of myotubular myopathy. We hope understanding the molecular pathways involving these miRNA-mRNA networks, which are disrupted in myotubular myopathy, will contribute to uncovering the mechanisms of muscle development and maintenance and the development of new therapies for myotubular myopathy.Resumo alargado em português disponível no documentoBeggs, Alan H,Oom, Maria do Mar Jácome FélixRepositório da Universidade de LisboaFontes, Mariana Miranda2010-07-27T08:58:30Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdftext/xmlhttp://hdl.handle.net/10451/1471enghttp://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000572632info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:41:01Zoai:repositorio.ul.pt:10451/1471Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:28:06.521038Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The role of microRNAs in X-linked myotubular myopathy
title The role of microRNAs in X-linked myotubular myopathy
spellingShingle The role of microRNAs in X-linked myotubular myopathy
Fontes, Mariana Miranda
Biologia molecular
Miopatia miotubular
Teses de mestrado
title_short The role of microRNAs in X-linked myotubular myopathy
title_full The role of microRNAs in X-linked myotubular myopathy
title_fullStr The role of microRNAs in X-linked myotubular myopathy
title_full_unstemmed The role of microRNAs in X-linked myotubular myopathy
title_sort The role of microRNAs in X-linked myotubular myopathy
author Fontes, Mariana Miranda
author_facet Fontes, Mariana Miranda
author_role author
dc.contributor.none.fl_str_mv Beggs, Alan H,
Oom, Maria do Mar Jácome Félix
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Fontes, Mariana Miranda
dc.subject.por.fl_str_mv Biologia molecular
Miopatia miotubular
Teses de mestrado
topic Biologia molecular
Miopatia miotubular
Teses de mestrado
description Tese de mestrado, Biologia (Bioplogia Humana e Ambiente), 2009, Universidade de Lisboa, Faculdade de Ciências
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01T00:00:00Z
2010-07-27T08:58:30Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/1471
url http://hdl.handle.net/10451/1471
dc.language.iso.fl_str_mv eng
language eng
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