研究進展
2012年8月31日，澳大利亞研究人員發現，通過阻斷小鼠子宮內一種稱為Grb10的蛋白質的功能，這些小鼠比正常老鼠具有更加強大更加多的肌肉。這一研究發現將刊登在2012年9月發行的 FASEB Journal雜誌上。該研究結論對如肌肉萎縮症、2型糖尿病、肌肉炎症所產生的一些列問具有重要意義。
發現這一種新的調節肌肉發育的機制，為開發潛在增加肌肉質量提供了新策略。歸根結底這項研究可能會改善肌肉萎縮以及代謝性疾病如2型糖尿病的治療效果。在這項研究中，Holt和他的同事比較了兩組老鼠。
一組小鼠中斷Grb10基因組，結果肌肉非常發達。另一組老鼠Grb10基因功能正常，結果肌肉沒什麼明顯變化。研究人員研究了成年和新生小鼠的肌肉特性後發現，Grb10功能缺失所造成肌肉的變化主要發生小鼠胎兒期發育階段。這些結果證實了Grb10可能改變肌肉的生長並促進癒合、肌肉再生和修復過程。
英文報告
doi:10.1096/fj.11-199349
PMC:
PMID:
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.
