2012年8月31日 讯 /生物谷BIOON/ --澳大利亚研究人员发现，通过阻断小鼠子宫内一种称为Grb10的蛋白质的功能，这些小鼠比正常老鼠具有更加强大更加多的肌肉。这一研究发现将刊登在2012年9月发行的FASEB Journal杂志上。该研究结论对如肌肉萎缩症、2型糖尿病、肌肉炎症所产生的一些列问具有重要意义。
Lowenna J. Holt博士说：发现这一种新的调节肌肉发育的机制，我们的研究工作为开发潜在增加肌肉质量提供了新策略。 归根结底这项研究可能会改善肌肉萎缩以及代谢性疾病如2型糖尿病的治疗效果。在这项研究中，Holt和他的同事比较了两组老鼠。
一组小鼠中断Grb10基因组，结果肌肉非常发达。另一组老鼠Grb10基因功能正常，结果肌肉没什么明显变化。研究人员研究了成年和新生小鼠的肌肉特性后发现，Grb10功能缺失所造成肌肉的变化主要发生小鼠胎儿期发育阶段。这些结果证实了Grb10可能改变肌肉的生长并促进愈合、肌肉再生和修复过程。（生物谷：Bioon.com）
doi:10.1096/fj.11-199349
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Grb10 regulates the development of fiber number in skeletal muscle
Lowenna J. Holt, Nigel Turner, Nancy Mokbel, Sophie Trefely, Timo Kanzleiter, Warren Kaplan, Christopher J. Ormandy, Roger J. Daly, and Gregory J. Cooney
Grb10 is an intracellular adaptor protein that acts as a negative regulator of insulin and insulin-like growth factor 1 (IGF1) receptors. Since global deletion of Grb10 in mice causes hypermuscularity, we have characterized the skeletal muscle physiology underlying this phenotype. Compared to wild-type (WT) controls, adult mice deficient in Grb10 have elevated body mass and muscle mass throughout adulthood, up to 12 mo of age. The muscle enlargement is not due to increased myofiber size, but rather an increase in myofiber number (142% of WT, P<0.01). There is no change in myofiber type proportions between WT and Grb10-deficient muscles, nor are the metabolic properties of the muscles altered on Grb10 deletion. Notably, the weight and cross-sectional area of hindlimbs from neonatal mice are increased in Grb10-deficient animals (198 and 137% of WT, respectively, both P<0.001). Functional gene signatures for myogenic signaling and proliferation are up-regulated in Grb10-deficient neonatal muscle. Our findings indicate that Grb10 plays a previously unrecognized role in regulating the development of fiber number during murine embryonic growth. In addition, Grb10-ablated muscle from adult mice shows coordinate gene changes that oppose those of muscle wasting pathologies, highlighting Grb10 as a potential therapeutic target for these conditions.—Holt, L. J., Turner, N., Mokbel, N., Trefely, S., Kanzleiter, T., Kaplan, W., Ormandy, C. J., Daly, R. J., Cooney, G. J. Grb10 regulates the development of fiber number in skeletal muscle.
