MYOGENIN GENE DISRUPTION RESULTS IN PERINATAL LETHALITY BECAUSE OF SEVERE MUSCLE DEFECT

MYOGENIN is a member of the basic helix-loop-helix (bHLH) gene family and converts multipotential mesodermal cells to myoblasts1-4. The four members of the myoD family show unique spatio-temporal expression pat terns5 and therefore may have different functions during myogenesis. H ere we inactivate the myogenin gene in order to understand its role in myogenesis. Homozygous mutations are lethal perinatally owing to the resulting major defects in skeletal muscle. The extent of disorganizat ion of muscle tissue differs in three regions. In the latero-ventral b ody wall, most cells, including myogenic cells, disappear and there is rapid accretion of fluid. In the limbs, cells of the myogenic lineage exist, but they are severely disrupted, and some of them are mono-nuc leate with properties of myoblasts. In contrast, there are many axial, intercostal and back muscle fibres to be seen, although fibres are ma inly disorganized and Z-lines are not present in most myofibrils. Thes e findings are evidence that myogenin is crucial for muscle developmen t in utero and demonstrate that other members of the myogenic gene fam ily cannot compensate for the defect.