Functional analysis of Lbx1 in muscles of chimeric mice

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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.