Olfactory ensheathing cells (OECs) prepared from the olfactory bulbs of adult transgenic Sprague Dawley (SD) rats expressing green fluorescent protein (GFP) were transplanted into a dorsal spinal cord transection lesion of SD rats. Five weeks after transplantation, the cells survived within the lesion zone and oriented longitudinally along axons that bridged the transection site. Although the highest density of GFP cells was within the lesion zone, some cells distributed longitudinally outside of the lesion area. Myelinated axons spanning the lesion were observed in discrete bundles encapsulated by a cellular element. Electron micrographs of spinal cords immunostained with an anti-GFP antibody indicated that a majority of the peripheral-like myelinated axons were derived from donor OECs. Open-field locomotor behavior was significantly improved in the OEC transplantation group. Thus, transplanted OECs derived from the adult olfactory bulb can survive and orient longitudinally across a spinal cord transection site and form myelin. This pattern of repair is associated with improved locomotion.

NKX3.1, a gene mapped to 8p21, is a member of the NK class of homeodomain proteins and is expressed primarily in the prostate. NKX3.1 exerts a growth-suppressive and differentiating effect on prostate epithelial cells. Because of its known functions and its location within a chromosomal region where evidence for prostate cancer linkage and somatic loss of heterozygosity is found, we hypothesize that sequence variants in the NKX3.1 gene increase prostate cancer risk. To address this, we first resequenced the NKX3.1 gene in 159 probands of hereditary prostate cancer families recruited at Johns Hopkins Hospital; each family has at least three first-degree relatives affected with prostate cancer. Twenty-one germ-line variants were identified in this analysis, including one previously described common nonsynonymous change (R52C), two novel rare nonsynonymous changes (A17T and T164A), and a novel common 18-bp deletion in the promoter. Overall, the germline variants were significantly linked to prostate cancer, with a peak heterogeneity logarithm of odds of 2.04 (P = 0.002) at the NKX3.1 gene. The rare nonsynonymous change, T164A, located in the homeobox domain of the gene, segregated with prostate cancer in a family with three affected brothers and one unaffected brother. Importantly, nuclear magnetic resonance solution structure analysis and circular dichroism studies showed this specific mutation to affect the stability of the homeodomain of the NKX3.1 protein and decreased binding to its cognate DNA recognition sequence. These results suggest that germ-line sequence variants in NKX3

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