Cargando…

Target genes of myostatin loss-of-function in muscles of late bovine fetuses

BACKGROUND: Myostatin, a muscle-specific member of the Transforming Growth Factor beta family, negatively regulates muscle development. Double-muscled (DM) cattle have a loss-of-function mutation in their myostatin gene responsible for the hypermuscular phenotype. Thus, these animals are a good mode...

Descripción completa

Detalles Bibliográficos
Autores principales: Cassar-Malek, Isabelle, Passelaigue, Florent, Bernard, Carine, Léger, Jean, Hocquette, Jean-François
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831773/
https://www.ncbi.nlm.nih.gov/pubmed/17331240
http://dx.doi.org/10.1186/1471-2164-8-63
_version_ 1782132795078868992
author Cassar-Malek, Isabelle
Passelaigue, Florent
Bernard, Carine
Léger, Jean
Hocquette, Jean-François
author_facet Cassar-Malek, Isabelle
Passelaigue, Florent
Bernard, Carine
Léger, Jean
Hocquette, Jean-François
author_sort Cassar-Malek, Isabelle
collection PubMed
description BACKGROUND: Myostatin, a muscle-specific member of the Transforming Growth Factor beta family, negatively regulates muscle development. Double-muscled (DM) cattle have a loss-of-function mutation in their myostatin gene responsible for the hypermuscular phenotype. Thus, these animals are a good model for understanding the mechanisms underpinning muscular hypertrophy. In order to identify individual genes or networks that may be myostatin targets, we looked for genes that were differentially expressed between DM and normal (NM) animals (n = 3 per group) in the semitendinosus muscle (hypertrophied in DM animals) at 260 days of fetal development (when the biochemical differentiation of muscle is intensive). A heterologous microarray (human and murine oligonucleotide sequences) of around 6,000 genes expressed in muscle was used. RESULTS: Many genes were found to be differentially expressed according to genetic type (some with a more than 5-fold change), and according to the presence of one or two functional myostatin allele(s). They belonged to various functional categories. The genes down-regulated in DM fetuses were mainly those encoding extracellular matrix proteins, slow contractile proteins and ribosomal proteins. The genes up-regulated in DM fetuses were mainly involved in the regulation of transcription, cell cycle/apoptosis, translation or DNA metabolism. These data highlight features indicating that DM muscle is shifted towards a more glycolytic metabolism, and has an altered extracellular matrix composition (e.g. down-regulation of COL1A1 and COL1A2, and up-regulation of COL4A2) and decreased adipocyte differentiation (down-regulation of C1QTNF3). The altered gene expression in the three major muscle compartments (fibers, connective tissue and intramuscular adipose tissue) is consistent with the well-known characteristics of DM cattle. In addition, novel potential targets of the myostatin gene were identified (MB, PLN, troponins, ZFHX1B). CONCLUSION: Thus, the myostatin loss-of-function mutation affected several physiological processes involved in the development and determination of the functional characteristics of muscle tissue.
format Text
id pubmed-1831773
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-18317732007-03-24 Target genes of myostatin loss-of-function in muscles of late bovine fetuses Cassar-Malek, Isabelle Passelaigue, Florent Bernard, Carine Léger, Jean Hocquette, Jean-François BMC Genomics Research Article BACKGROUND: Myostatin, a muscle-specific member of the Transforming Growth Factor beta family, negatively regulates muscle development. Double-muscled (DM) cattle have a loss-of-function mutation in their myostatin gene responsible for the hypermuscular phenotype. Thus, these animals are a good model for understanding the mechanisms underpinning muscular hypertrophy. In order to identify individual genes or networks that may be myostatin targets, we looked for genes that were differentially expressed between DM and normal (NM) animals (n = 3 per group) in the semitendinosus muscle (hypertrophied in DM animals) at 260 days of fetal development (when the biochemical differentiation of muscle is intensive). A heterologous microarray (human and murine oligonucleotide sequences) of around 6,000 genes expressed in muscle was used. RESULTS: Many genes were found to be differentially expressed according to genetic type (some with a more than 5-fold change), and according to the presence of one or two functional myostatin allele(s). They belonged to various functional categories. The genes down-regulated in DM fetuses were mainly those encoding extracellular matrix proteins, slow contractile proteins and ribosomal proteins. The genes up-regulated in DM fetuses were mainly involved in the regulation of transcription, cell cycle/apoptosis, translation or DNA metabolism. These data highlight features indicating that DM muscle is shifted towards a more glycolytic metabolism, and has an altered extracellular matrix composition (e.g. down-regulation of COL1A1 and COL1A2, and up-regulation of COL4A2) and decreased adipocyte differentiation (down-regulation of C1QTNF3). The altered gene expression in the three major muscle compartments (fibers, connective tissue and intramuscular adipose tissue) is consistent with the well-known characteristics of DM cattle. In addition, novel potential targets of the myostatin gene were identified (MB, PLN, troponins, ZFHX1B). CONCLUSION: Thus, the myostatin loss-of-function mutation affected several physiological processes involved in the development and determination of the functional characteristics of muscle tissue. BioMed Central 2007-03-01 /pmc/articles/PMC1831773/ /pubmed/17331240 http://dx.doi.org/10.1186/1471-2164-8-63 Text en Copyright © 2007 Cassar-Malek et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cassar-Malek, Isabelle
Passelaigue, Florent
Bernard, Carine
Léger, Jean
Hocquette, Jean-François
Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title_full Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title_fullStr Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title_full_unstemmed Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title_short Target genes of myostatin loss-of-function in muscles of late bovine fetuses
title_sort target genes of myostatin loss-of-function in muscles of late bovine fetuses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831773/
https://www.ncbi.nlm.nih.gov/pubmed/17331240
http://dx.doi.org/10.1186/1471-2164-8-63
work_keys_str_mv AT cassarmalekisabelle targetgenesofmyostatinlossoffunctioninmusclesoflatebovinefetuses
AT passelaigueflorent targetgenesofmyostatinlossoffunctioninmusclesoflatebovinefetuses
AT bernardcarine targetgenesofmyostatinlossoffunctioninmusclesoflatebovinefetuses
AT legerjean targetgenesofmyostatinlossoffunctioninmusclesoflatebovinefetuses
AT hocquettejeanfrancois targetgenesofmyostatinlossoffunctioninmusclesoflatebovinefetuses