Jacob Dena A, Bengston C Lynn, Forger Nancy G
Department of Psychology and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Neurosci. 2005 Jun 8;25(23):5638-44. doi: 10.1523/JNEUROSCI.1200-05.2005.
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.
球海绵体肌脊髓核（SNB）中的运动神经元及其在会阴区的靶肌肉，即球海绵体肌（BC）和肛提肌（LA），在雌性啮齿动物中通常会退化。在出生前后进行雄激素处理可防止运动神经元和肌肉死亡。为了确定该神经肌肉系统激素依赖性存活的细胞内机制，我们研究了促死亡基因Bax靶向缺失的小鼠。无论是使用运动神经元特异性标记物进行免疫标记，还是用荧光示踪剂Fluoro-Gold进行逆行标记，雌性Bax-/-小鼠的SNB运动神经元数量均增加。基于逆行追踪，Bax-/-小鼠中SNB细胞数量的性别差异消失。因此，Bax是SNB中性别二态性运动神经元死亡所必需的，并且通过缺失Bax而获救的运动神经元将其轴突投射到外周。然而，Bax-/-雌性小鼠SNB中的平均胞体大小减小，并且雌性基因敲除小鼠的SNB中有一小部分非常小的细胞。此外，无论Bax基因状态如何，在任何雌性小鼠中均未发现BC肌肉。所有雌性小鼠都有一小块LA肌肉，并且缺失Bax导致雌性小鼠LA纤维数量增加两倍。然而，相对于LA肌肉纤维数量>50倍的性别差异，这种增加很小。因此，会阴肌的性别差异大多不受Bax蛋白缺失的影响，并且在Bax-/-动物中SNB运动神经元数量与靶肌肉大小无关。
