Murchison Nicholas D, Price Brian A, Conner David A, Keene Douglas R, Olson Eric N, Tabin Clifford J, Schweitzer Ronen
Shriners Hospital for Children, Research Division, Portland, OR 97239, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Development. 2007 Jul;134(14):2697-708. doi: 10.1242/dev.001933. Epub 2007 Jun 13.
The scleraxis (Scx) gene, encoding a bHLH transcription factor, is expressed in the progenitors and cells of all tendon tissues. To determine Scx function, we produced a mutant null allele. Scx-/- mice were viable, but showed severe tendon defects, which manifested in a drastically limited use of all paws and back muscles and a complete inability to move the tail. Interestingly, although the differentiation of all force-transmitting and intermuscular tendons was disrupted, other categories of tendons, the function of which is mainly to anchor muscles to the skeleton, were less affected and remained functional, enabling the viability of Scx-/- mutants. The force-transmitting tendons of the limbs and tail varied in the severity to which they were affected, ranging from dramatic failure of progenitor differentiation resulting in the loss of segments or complete tendons, to the formation of small and poorly organized tendons. Tendon progenitors appeared normal in Scx-/- embryos and a phenotype resulting from a failure in the condensation of tendon progenitors to give rise to distinct tendons was first detected at embryonic day (E)13.5. In the tendons that persisted in Scx-/- mutants, we found a reduced and less organized tendon matrix and disorganization at the cellular level that led to intermixing of tenocytes and endotenon cells. The phenotype of Scx-/- mutants emphasizes the diversity of tendon tissues and represents the first molecular insight into the important process of tendon differentiation.
硬骨素（Scx）基因编码一种bHLH转录因子，在所有肌腱组织的祖细胞和细胞中表达。为了确定Scx的功能，我们构建了一个无效突变等位基因。Scx基因敲除小鼠能够存活，但表现出严重的肌腱缺陷，表现为所有爪子和背部肌肉的使用严重受限，完全无法移动尾巴。有趣的是，尽管所有传递力的肌腱和肌间肌腱的分化都受到破坏，但其他类型的肌腱，其主要功能是将肌肉附着于骨骼，受影响较小且仍保持功能，这使得Scx基因敲除突变体能够存活。四肢和尾巴的传递力肌腱受影响的严重程度各不相同，从祖细胞分化严重失败导致节段或完整肌腱缺失，到形成小而结构不良的肌腱。在Scx基因敲除胚胎中，肌腱祖细胞看起来正常，肌腱祖细胞凝聚失败导致无法形成明显肌腱的表型最早在胚胎第13.5天被检测到。在Scx基因敲除突变体中持续存在的肌腱中，我们发现肌腱基质减少且结构紊乱，细胞水平上也紊乱，导致腱细胞和腱内膜细胞相互混合。Scx基因敲除突变体的表型强调了肌腱组织的多样性，并代表了对肌腱分化这一重要过程的首次分子见解。
