Functional analysis of Lbx1 in muscles of chimeric mice

Lbx 1是一种小鼠同源异型盒基因，在形成肢体、隔膜和舌的肌肉组织的迁移性成肌细胞中表达，但在躯干水平的肌节中的非迁移性成肌细胞中不表达。这种特异性表达模式表明Lbx 1可能在迁移性成肌细胞的特化和分化中起关键作用。为了阐明Lbx 1的功能，我们使用LacZ标记的ES细胞在肌细胞生成素启动子的控制下携带Lbx 1产生嵌合小鼠。在这样的嵌合体中，我们没有检测到胚胎发生过程中迁移成肌细胞的任何异常行为。然而，出生后两周，这些嵌合体小鼠在四肢和背部肌肉中表现出明显的形态异常。观察到肌纤维大小不规则，存在巨纤维、中央放置的核、螺旋纤维、坏死和吞噬作用，所有这些都被认为是肌肉变性-再生发生的迹象。这些受损的肌肉被发现总是与ES-衍生细胞的贡献，并且损伤的程度与ES-衍生细胞的贡献率成比例。在这里，我们展示了嵌合小鼠有趣的表型，这可能是一个线索，以了解Lbx 1如何在肌肉发生过程中的功能。

Lbx1, a mouse homeobox gene, is expressed in migratory myoblasts that form musculature of limb, diaphragm, and tongue but not expressed in non-migratory myoblasts in the myotomes at the trunk level. This specific expression patterns suggest that Lbx1 may play a key role in specification and differentiation of migratory myoblasts. To clarify the function of Lbx1, we generated chimeric mice using LacZ labelled-ES cells carrying Lbxl under the control of myogenin promoter. In such chimeras, we did not detect any abnormal behavior of migrating myoblasts during embryogenesis. Two weeks after birth, however, these chimeric mice exhibited obvious morphological abnormalities in limb and back muscles. Irregularity in the sizes of the muscle fibers with presence of giant fibers, centrally placed nuclei, whorled fibers, necrosis and phagocytosis, all of which are known as signs of muscle degeneration-regeneration occurring, were observed. These impaired muscles were found to be always contributed with the ES-derived cells, and the extent of damage was in proportion to the contribution rate of the ES-derived cells. Here, we demonstrate interesting phenotypes of the chimeric mice, which may be a cue to understand how Lbx1 functions during myogenesis.