07-P005 – Withdrawn

Previous studies have demonstrated that depletion of Gas7 impedes neurite outgrowth in primary cultures of Purkinje neurons, and that Gas7 promotes neurite outgrowth in PC12 cells. To investigate the physiological function of Gas7, we generated by homologous recombination a Gas7-mutant mouse which produced a Gas7 variant protein with an in-frame deletion of amino acid residues 103–120. Only low levels of the Gas7 variant protein were found in the mutant mice because of a shortened protein half-life. In comparison with the wild type, mutant mice had reduced motor activity and muscle strength which could be ascribed to deficits in skeletal muscle fast-twitch fibers, with a much smaller proportion of the IIa/x myofiber subtype found in the soleus. Gross morphological features of the neuromuscular junction including the pattern of axon terminal branches and the shape of AChR clusters in the soleus remained generally unchanged between the wild type and mutant mice, though endplate average size and nAChR transcription levels rose in the mutant. Gas7 variant protein was localized in the terminal Schwann cells and in the presynaptic region of motor axons, a similar pattern to the wild-type Gas7, but at lower levels. This is the first evidence that Gas7 is expressed not only in central neurons, but also in Schwann cells and output axons of the peripheral nervous system. The results also suggest that Gas7 may control AChR expression or clustering and thus affect muscle strength and motor activity.