title: Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice.
abstract: Syncytins are envelope genes from endogenous retroviruses, "captured" for a role in placentation. They mediate cell-cell fusion, resulting in the formation of a syncytium (the syncytiotrophoblast) at the fetomaternal interface. These genes have been found in all placental mammals in which they have been searched for. Cell-cell fusion is also pivotal for muscle fiber formation and repair, where the myotubes are formed from the fusion of mononucleated myoblasts into large multinucleated structures. Here we show, taking advantage of mice knocked out for syncytins, that these captured genes contribute to myoblast fusion, with a >20% reduction in muscle mass, mean muscle fiber area and number of nuclei per fiber in knocked out mice for one of the two murine syncytin genes. Remarkably, this reduction is only observed in males, which subsequently show muscle quantitative traits more similar to those of females. In addition, we show that syncytins also contribute to muscle repair after cardiotoxin-induced injury, with again a male-specific effect on the rate and extent of regeneration. Finally, ex vivo experiments carried out on murine myoblasts demonstrate the direct involvement of syncytins in fusion, with a >40% reduction in fusion index upon addition of siRNA against both syncytins. Importantly, similar effects are observed with primary myoblasts from sheep, dog and human, with a 20-40% reduction upon addition of siRNA against the corresponding syncytins. Altogether, these results show a direct contribution of the fusogenic syncytins to myogenesis, with a demonstrated male-dependence of the effect in mice, suggesting that these captured genes could be responsible for the muscle sexual dimorphism observed in placental mammals.
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: François
authors: 0000-0003-3263-2961
authors: F
authors: Redelsperger
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: Najat
authors: N
authors: Raddi
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: Agathe
authors: A
authors: Bacquin
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: Cécile
authors: C
authors: Vernochet
authors: UPMC Université-Paris 6, UM 76, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.|Institut de Myologie, Paris, France.
authors: Virginie
authors: V
authors: Mariot
authors: INSERM IMRB U955-E10, Créteil, France.|Université Paris-Est, Ecole nationale vétérinaire d'Alfort, Maisons-Alfort, France.|Université Paris-Est Créteil, Faculté de médecine, Créteil, France.
authors: Vincent
authors: V
authors: Gache
authors: INSERM IMRB U955-E10, Créteil, France.|Université Paris-Est, Ecole nationale vétérinaire d'Alfort, Maisons-Alfort, France.|Université Paris-Est Créteil, Faculté de médecine, Créteil, France.
authors: Nicolas
authors: 0000-0003-4719-3834
authors: N
authors: Blanchard-Gutton
authors: INSERM U935, Villejuif, France.|Université Paris-Sud, Institut André Lwoff, Villejuif, France.
authors: Stéphanie
authors: S
authors: Charrin
authors: INSERM IMRB U955-E10, Créteil, France.|Université Paris-Est, Ecole nationale vétérinaire d'Alfort, Maisons-Alfort, France.|Université Paris-Est Créteil, Faculté de médecine, Créteil, France.
authors: Laurent
authors: L
authors: Tiret
authors: UPMC Université-Paris 6, UM 76, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.|Institut de Myologie, Paris, France.
authors: Julie
authors: J
authors: Dumonceaux
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: Anne
authors: A
authors: Dupressoir
authors: Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, CNRS UMR 9196, Institut Gustave Roussy, Villejuif, France.|Université Paris-Sud, Orsay, France.
authors: Thierry
authors: T
authors: Heidmann
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004285:Dogs; D020077:Endogenous Retroviruses / Q000235:genetics; D005260:Female; D055786:Gene Knockout Techniques; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008322:Mammals; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; C405335:syncytin