Immunohistochemical expression of P400 protein in Purkinje cells of sphingomyelinosis mouse.

Immunohistochemical expression of P400 protein, a glycoprotein localized to the Purkinje cell membrane, has been studied in the cerebellum of spm mouse using anti-P400 monoclonal antibody. The initial change observed in the Purkinje cells was a swelling of the cell body with distortion of the neurites; this occurred as early as 5 weeks of age. A significant, patchy loss of Purkinje cells started at 6 weeks before cerebellar signs became manifest. With progression of the disease the dendritic processes in the molecular layer showed a marked swelling, followed by irregular arborization and finally by disintegration. A few, heterotopic Purkinje cells were found in the subcortical white matter; this was interpreted as an indication that a disturbance in neuronal migration could be superimposed on the sphingolipid metabolic disorder. Additionally, P400-immunoreactive nerve cells were occasionally encountered in areas of the deep cerebellar nuclei and in the lateral vestibular nuclei of the pontine tegmentum. The number of P400-immunoreactive Purkinje cells correlated well with the percentages of the remaining Purkinje cells during the ages of 4 to 7 wks. At the late stage of 10 to 12 weeks almost all Purkinje cells had lost their P400-immunoreactivity. It is suggested that Purkinje cells that fail to express P400 protein may undergo an immunohistochemical degeneration of the plasma membrane.