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Volume 17, Number 24, Issue of December 15, 1997 pp. 9605-9612

Sexual Dimorphism in the Spinal Cord Is Absent in Mice Lacking the Ciliary Neurotrophic Factor Receptor

Received July 15, 1997; revised Sept. 15, 1997; accepted Sept. 26, 1997.

Nancy G. Forger¹, Michelle L. Howell¹, Lynn Bengston¹, Laura MacKenzie¹, Thomas M. DeChiara², and George D. Yancopoulos²

¹ Department of Psychology and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, and ² Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, New York 10591

Ciliary neurotrophic factor (CNTF) has potent survival-promoting effects on motoneurons in vitro and in vivo. We examined knockout mice with null mutations of the gene for either CNTF itself or the -subunit of the CNTF receptor (CNTFR) to assess whether CNTF and/or its receptors are involved in the development of a sexually dimorphic neuromuscular system. Male rodents have many more motoneurons in the spinal nucleus of the bulbocavernosus (SNB) than do females. This sex difference is caused by hormone-regulated death of SNB motoneurons and their target muscles. Sexual dimorphism of SNB motoneuron number developed completely normally in CNTF knockout (CNTF /) mice. In contrast, a sex difference in the SNB was absent in CNTFR / animals: male mice lacking a functional CNTF -receptor had fewer than half as many SNB motoneurons than did wild-type males and no more than did their female counterparts. Size of the bulbocavernosus and levator ani muscles, the main targets of SNB motoneurons, was not affected in either CNTF or CNTFR knockout males. These observations suggest that signaling through the CNTF receptor is involved in sexually dimorphic development of SNB motoneuron number and that target muscle survival per se is not sufficient to ensure motoneuron survival in this system. In addition, our observations are consistent with the suggestion that CNTF 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.

Key words: motoneuron; androgen; sexual dimorphism; ciliary neurotrophic factor; knockout mice; androgen

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