PTPzeta/RPTPbeta is a receptor-like protein tyrosine phosphatase expressed as a chondroitin sulfate proteoglycan. We generated mice in which the PTPzeta gene was replaced by the LacZ gene by gene targeting. Analysis of heterozygous PTPzeta-targeted mice allowed us to identify PTPzeta-producing cells during development by examining expression of the LacZ gene. LacZ expression was detected only in the central nervous system throughout development from embryonic day 8.5. In the postnatal period, subsets of neurons and astrocytes in the brain, including pyramidal cells and astrocytes in the hippocampus, expressed LacZ. Primary cultures of cells from the cerebral cortex of embryonic day 16 mice also indicated that both neurons and astrocytes were positive for LacZ. These results indicated that neurons and astrocytes express PTPzeta.