Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture and structural abnormalities in the...

Protein tyrosine phosphatase sigma (PTPsigma) is a member of the LAR family of receptor tyrosine phosphatases and is highly expressed in the nervous system during development. PTPsigma is homologous to the Drosophila DLAR, which plays a key role in the targeting of axonal growth cones in flies. We have previously inactivated the Ptprs gene in mice and demonstrated stunted growth, developmental delays, and neurological and neuroendocrine defects in the PTPsigma null animals. Here, we mapped the expression of the lac-Z reporter gene included in the knockout cassette and surveyed the development of the CNS in these mice after birth. The strongest expression of beta-galactosidase (PTPsigma) was observed in the hippocampus, cerebral cortex, olfactory bulbs, and subependymal layer. Our analysis reveals hippocampal dysgenesis, reductions in the thickness of the corpus callosum and the cerebral cortex, and late expression of the growth-associated protein 43 (GAP-43) in the knockout animals. Architectural abnormalities in the brain and spinal cord were confirmed by immunoreactivity to neurofilament and glial fibrillary acidic protein (GFAP) antibodies. Several of these neural abnormalities were corrected with age, suggesting a delay in neurological development related to the knockout of the Ptprs gene. These data suggest that PTPsigma is likely involved in neurogenesis, axonal growth, and axonal pathfinding in the maturation of the mammalian CNS.