Mice Deficient in the Polysialyltransferase ST8SiaIV/PST-1 Allow Discrimination of the Roles of Neural Cell Adhesion Molecule Protein and Polysialic Acid in Neural Development and Synaptic Plasticity

摘要: Functional properties of the neural cell adhesion molecule (NCAM) are strongly influenced by polysialylation. We used gene-targeting to generate mice lacking ST8SiaIV/PST-1, one polysialyltransferases responsible for addition polysialic acid (PSA) NCAM. Mice homozygous null mutation reveal normal development gross anatomical features. In contrast NCAM-deficient mice, olfactory precursor cells in rostral migratory stream express PSA and follow their pathway. Furthermore, delamination mossy fibers hippocampal CA3 region, as found does not occur ST8SiaIV mutants. However, during postnatal these animals show a decrease most brain regions compared wild-type animals. Loss presence NCAM protein but absence obvious histological changes allowed us directly address role synaptic plasticity. Schaffer collateral-CA1 synapses, which wild types, showed impaired long-term potentiation (LTP) depression (LTD) adult This impairment was age-dependent, following time course developmental disappearance PSA. Contrary mutant LTP mutants undisturbed at fiber–CA3 do mice. The results demonstrate an essential plasticity CA1 whereas produced different polysialyltransferase or early stages differentiation regulates migration correct lamination fibers. suggest that is likely be important region.