SEXUAL DIMORPHISM IN THE SPINAL-CORD IS ABSENT IN MICE LACKING THE CILIARY NEUROTROPHIC FACTOR-RECEPTOR

Ciliary neurotrophic factor (CNTF) has potent survival-promoting effec ts on motoneurons in vitro and in vivo. We examined knockout mice with null mutations of the gene for either CNTF itself or the alpha-subuni t of the CNTF receptor (CNTFR alpha) to assess whether CNTF and/or its receptors are involved in the development of a sexually dimorphic neu romuscular system. Male rodents have many more motoneurons in the spin al nucleus of the bulbocavernosus (SNB) than do females. This sex diff erence is caused by hormone-regulated death of SNB motoneurons and the ir target muscles. Sexual dimorphism of SNB motoneuron number develope d completely normally in CNTF knockout (CNTF -/-) mice. In contrast, a sex difference in the SNB was absent in CNTFR alpha -/- animals: male mice lacking a functional CNTF alpha-receptor had fewer than half as many SNB motoneurons than did wild-type males and no more than did the ir female counterparts. Size of the bulbocavernosus and levator ani mu scles, the main targets of SNB motoneurons, was not affected in either CNTF or CNTFR alpha knockout males. These observations suggest that s ignaling through the CNTF receptor is involved in sexually dimorphic d evelopment of SNB motoneuron number and that target muscle survival pe r se is not sufficient to ensure motoneuron survival in this system. I n addition, our observations are consistent with the suggestion that C NTF itself is not the only endogenous ligand for the CNTF receptor. A second, as yet unknown, ligand may be important for neural development , including sexually dimorphic motoneuron development.