Neural cell adhesion molecule and D3 protein in the cerebellum of weaver mutant mice

Weaver (wv/wv) mutant mice are characterized by extensive granule cell degeneration and can therefore be used as a model for brain degeneration that does not involve blood-brain barrier damage. The ontogeny of the neural cell adhesion molecule (NCAM) and the neuronal antigen D3 protein were investigated in cerebellum and forebrain of weaver mutant mice up to post-natal day 60. In the forebrain the concentration of both proteins was virtually unchanged. In cerebellum, in contrast, the concentration of D3 decreased markedly whereas that of NCAM remained unchanged. Similar findings were obtained at post-natal day 30 in the cerebellum of other neurologic mutants, namely the staggerer (sg/sg) and reeler (rl/rl). At this age the concentration of a synaptic vesicle marker, synaptophysin, was severely decreased in the cerebellum of all three mutants. The concentration of neuron-specific enolase was less affected, whereas the concentrations of the glial markers glutamine synthetase and glial fibrillary acidic protein were both increased. The NCAM/D3 concentration ratio, which probably reflects the ongoing rate of synaptic remodelling, was increased during the whole ontogeny of weaver mutant mice as compared with heterozygous controls. At post-natal day 30, the ratio was increased by 180% in weaver, by 170% in staggerer and by 60% in reeler cerebellum. These findings lend further support to the usefulness of the NCAM/D3 ratio as a marker of neural plasticity and synaptic remodelling in both animals and man.