ROSTROCAUDAL EXPRESSION OF ANTIBODY HNK-1-REACTIVE GLYCOLIPIDS IN MOUSE CEREBELLUM - RELATIONSHIP TO DEVELOPMENTAL COMPARTMENTS AND LEANER MUTATION

Sulfoglucuronylglycolipids (SGGLs) and glycoproteins, reacting with mo noclonal antibody HNK-1, are developmentally and spatially regulated i n the mammalian cortex and cerebellum. It has been proposed that the H NK- 1 carbohydrate epitope is involved in intercellular adhesion and c ell-cell interactions. Biochemical analysis and immunocytochemical loc alization of SGGLs and other neolacto series glycolipids were studied in the leaner mutant mouse cerebellum, where a slow and progressive ro stral to caudal degeneration occurs with a gradual loss of both granul e cells and Purkinje cells. Biochemical analyses showed that SGGLs and other neolacto series of glycolipids were significantly decreased in the adult leaner cerebellum; however, HNK-1-reactive glycoproteins wer e not affected. By an immunocytochemical method which selectively loca lizes the lipid antigens, it is shown that SGGLs are primarily associa ted with Purkinje cell bodies and their dendrites in the molecular lay er and in cerebellar nuclei where Purkinje cell axons terminate. At po stnatal day 30 (P30), SGGL immunoreactivity (SGGL-ir) in the leaner ce rebellum was reduced moderately compared to normal littermates, which correlated with the minimal degree of Purkinje cell degeneration at th is age in leaner and with the biochemical data. At P67 and P90, the SG GL-ir was significantly more reduced in the leaner as Purkinje cell de generation proceeded. There was a direct correlation between loss of P urkinje cells and SGGL-ir in the cerebellar molecular layer. In both n ormal and young leaner cerebella, the SGGL-ir in different lobules was not uniform; there were distinct rostrocaudal and mediolateral differ ences. SGGL-ir was markedly more intense in rostral than in caudal lob ules in the vermis, the dividing line being the region immediately cau dal to the primary fissure and rostral to the declival sulcus. In the lateral cerebellum, the SGGL-ir was less intense than in the vermis an d the rostrocaudal difference was not as pronounced. There was also no nuniformity in the intensity of staining in different folia. The rostr ocaudal as well as mediolateral differences in the intensity of SGGL-i r were confirmed independently by biochemical analysis. The differenti al phenotypic expression of SGGLs and the selective susceptibility to Purkinje cell death in leaner mutant are discussed in relation to the known embryologic and ontogenetic compartmentation of cerebellum.