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 alpha-subunit of the CNTF receptor (CNTFRalpha) 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 CNTFRalpha -/- 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 their female counterparts. Size of the bulbocavernosus and levator ani muscles, the main targets of SNB motoneurons, was not affected in either CNTF or CNTFRalpha 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.

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exhibit an SLE-like autoimmune disease in which autoantibodies are a prominent feature. We analyzed the phenotype and T-cell receptor V]/ expression pattern in CD4 T cells of this mutant mouse strain to detect abnormalities that could explain the autoimmunity. The CD4 T cells contain two distinct abnormal populations. One of these expresses B220 and HSA, and in these and other respects closely resembles the accumulating CD4-CD8-population. The other expresses a high level of CD44 (Pgp-1), and a high level of the 16A epitope of CD45, and so resembles post-activation T cells. Both of these cell types are exclusive to MRL-Mp-lpr/lpr. We also identified V]/5-and V]/11-positive CD4+ T cells, in both MRL-Mp-lpr/lpr and MRL-Mp-+/+ mice. We conclude that autoimmune T cells can be detected in these mice, but that they are not the cause of the accumulation of abnormal CD4 and CD4-CD8-cells.