DISTRIBUTION OF A MURINE PROTEIN-TYROSINE-PHOSPHATASE BL-BETA-GALACTOSIDASE FUSION PROTEIN SUGGESTS A ROLE IN NEURITE OUTGROWTH

We have generated a gene trap insertion into the protein tyrosine phos phatase-BL (PTP-BL) locus, which produces a fusion of the N-terminal h alf of PTP-BL with beta-galactosidase, During development, beta-galact osidase activity was seen in all epithelial cells: strong staining was observed in the stomach and kidney epithelium, the ependymal layer of the central nervous system, and the surface ectoderm, Particularly pr ominent beta-galactosidase activity was seen in the peripheral nervous system, which correlated with neurite outgrowth, In epithelial cells, staining was seen in the apical portion of the cells. In nerves, beta -galactosidase activity was associated with growth cones as well as wi th Schwann cells. This suggests that the amino-terminal portion of PTP -BL contains sequences sufficient to target the fusion protein to spec ific subcellular compartments. In situ hybridization with a PTP-BL pro be demonstrated that all tissues in which beta-galactosidase activity was seen were genuine sites of expression of the PTP-BL gene, although differences in the stability of the PTP-BL protein and the PTP-BL-bet a-galactosidase fusion protein may exist. The distribution of beta-gal actosidase activity in the peripheral nervous system, together with th e structure of the wild-type protein, suggests that this phosphatase m ay have a role in regulation of the cytoskeleton during the developmen t of the peripheral nervous system. (C) 1998 Wiley-Liss, Inc.