Effects of Bax gene deletion on muscle and motoneuron degeneration in a sexually dimorphic neuromuscular system.

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target muscles in the perineum, bulbocavernosus (BC), and levator ani (LA) normally degenerate in female rodents. Death of the motoneurons and muscles can be prevented by androgen treatments around the time of birth. To identify the intracellular mechanisms underlying hormone-dependent survival of this neuromuscular system, we examined mice with a targeted disruption of the pro-death gene Bax. SNB motoneuron number was increased in female Bax-/- mice, whether measured using immunolabeling for a motoneuron-specific marker or retrograde labeling with the fluorescent tracer Fluoro-Gold. Based on retrograde tracing, the sex difference in SNB cell number is eliminated in Bax-/- mice. Thus, Bax is required for sexually dimorphic motoneuron death in the SNB, and motoneurons rescued by Bax deletion project their axons to the periphery. Mean soma size in the SNB of Bax-/- females is reduced, however, and there is a subpopulation of very small cells in the SNB of female knock-outs. In addition, the BC muscle was not identified in any female, regardless of Bax gene status. All females possessed a small LA muscle, and Bax deletion resulted in a tripling of LA fiber number in females. This increase was small, however, relative to the >50-fold sex difference in LA muscle fiber number. Thus, the sex difference in the perineal muscles is mostly unaffected by the absence of Bax protein, and SNB motoneuron number is dissociated from target muscle size in Bax-/- animals.