逆转录病毒在它们的表面上携带着蛋白来调节它们的包膜与靶细胞的细胞膜融合。一旦释放到靶细胞内，它们的遗传物质整合到宿主的染色体上。在罕见的情形下，被感染的靶细胞参与繁殖，这些病毒基因可能传递给它们的后代。因此，将近8%的哺乳动物基因组是由逆转录病毒的残留部分---或者说内源性逆转录病毒---组成的。它们当中的大多数是没有活性的，但是也有一些基因仍然能够表达蛋白，比如合胞素（syncytin），即存在所有哺乳动物中，由遗传自哺乳动物的祖先“捕获的”逆转录病毒的基因编码的蛋白。在5年前，通过在小鼠体内让这些基因失活，Heidmann团队已证实合胞素促进胎盘形成。鉴于合胞素具有介导细胞-细胞融合的能力，它们产生合胞体滋养层，即在母胎界面上，由来自胚胎的大量细胞融合在一起形成的一种组织。
在这项新的研究中，同样利用小鼠作为研究对象，Heidmann团队揭示出这些蛋白的一种“附带的”意料之外的影响：它们让雄性小鼠具有比雌性小鼠更多的肌纤维。就像合胞体滋养层一样，肌纤维是由肌肉干细胞融合产生的。在经过基因修饰让合胞素编码基因失活的雄性小鼠体内，它们的肌纤维相比正常的雄性小鼠变小了20%，而且它们的肌纤维中的细胞核数量也比正常的雄性小鼠少了20%；它们的肌纤维类似于在雌性小鼠中观察到的情形，而且它们的总肌肉质量也是类似的。因此，它似乎表明在肌肉生长期间，让合胞素失活导致肌肉干细胞融合缺失，而且仅仅是在雄性小鼠体内发生的。针对遭受损伤后肌肉再生而言，研究人员也观察到同样的现象：不能够产生合胞素的雄性小鼠要比正常的雄性小鼠具有更差的再生能力，但是与雌性小鼠的再生能力相当。再者，再生的肌纤维会产生合胞素，当然再次仅在雄性小鼠体内发生。
如果这一发现在其他的哺乳动物体内也被证实的话，那么它可能解释了雄性哺乳动物和雌性哺乳动物之间的肌肉二态性，而这一差异并没有在卵生动物中如此系统性地观察到。通过培养来自不同哺乳动物物种（小鼠、羊、狗和人）的肌肉干细胞，研究人员又取得进一步的进展：在所有测试的哺乳动物物种中，合胞素促进肌纤维形成。如今，在这些哺乳动物物种中，还需证实合胞素的作用是否也是雄性特异性的。（生物谷 Bioon.com）
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Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice
François Redelsperger, Najat Raddi , Agathe Bacquin , Cécile Vernochet, Virginie Mariot, Vincent Gache, Nicolas Blanchard-Gutton, Stéphanie Charrin, Laurent Tiret, Julie Dumonceaux, Anne Dupressoir, Thierry Heidmann
doi:10.1371/journal.pgen.1006289
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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.
