Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice.

Abstract

The neural cell adhesion molecule (N-CAM) has an unusually high amount of sialic acid (28-35 g/100 g of polypeptide) and shows microheterogeneity in electrophoretic gels in its embryonic or E form. During development, the molecule undergoes conversion to several adult or A forms, which resemble the E form but which on the average have only 10% sialic acid and do not appear to be microheterogeneous. In the study, rabbit antibodies to mouse N-CAM and 2 different monoclonal antibodies were used to follow the E .fwdarw. A conversion in normal and mutant mice. E .fwdarw. A conversion to 3 forms (Mr [molecular ratio] 180,000, Mr 140,000 and Mr 120,000) was found to occur at different rates in different parts of the brains of wild-type mice. Examination of the entire cerebellum of the granuloprival mouse mutant staggerer (sg/sg) showed that the E .fwdarw. A conversion did not occur by 21 days after birth, whereas in wild type it was almost complete at that time. There was also some delay in E .fwdarw. A conversion within the cerebral cortex of sg/sg, although phenotypically no evidence of cortical disorder was detected. In pooled tissues from phenotypically normal-appearing littermates (i.e., a mixture of sg/ + and +/+), a slight conversion delay was also found in cerebellum and cortex. The mutants weaver, reeler and jimpy all showed normal schedules of E .fwdarw. A conversion. A major defect in staggerer mutants may relate to a failure in local surface modulation of N-CAM to produce the A forms of the molecule. Some of the failures of synapse formation and of cell survival seen in this disease may result from the anomaly, which is likely to alter the binding properties of N-CAM at critical times of development.