Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma

Protein tyrosine phosphatase sigma (PTP-sigma, encoded by the Ptprs gene) i s a member of the LAR subfamily of receptor-like protein tyrosine phosphata ses that is highly expressed during mammalian embryonic development in the germinal cell layer lining the lateral ventricles of the developing brain, dorsal root ganglia, Rathke's pouch, olfactory epithelium, retina and devel oping lung and heart(1-4). On the basis of its expression and homology with the Drosophila melanogaster orthologues DPTP99 and DPTP100A (refs 5,6), wh ich have roles in the targeting of axonal growth cones, we hypothesized tha t PTP-sigma may also have a modulating function in cell-cell interactions, as well as in axon guidance during mammalian embryogenesis, To investigate its function in vivo, we generated Ptprs-deficient mice. The resulting Ptpr s(-/-) animals display retarded growth, increased neonatal mortality, hypos mia and hypofecundity. Anatomical and histological analyses showed a decrea se in overall brain size with a severe depletion of luteinizing hormone-rel easing hormone (LHRH)immunoreactive cells in Ptprs(-/-) hypothalamus. Ptprs (-/-) mice have an enlarged intermediate pituitary lobe, but smaller anteri or and posterior lobes, These results suggest that tyrosine phosphorylation -dependent signalling pathways regulated by PTP-sigma influence the prolife ration and/or adhesiveness of various cell types in the developing hypothal amo-pituitary axis.