Immunohistochemical Studies on Cerebellar Purkinje Cells of Patients with Menkes' Kinky Hair Disease

Immunohistochemical investigations were carried out on cerebellar Purkinje cells of eight patients with Menkes' kinky hair disease (MD) using an antibody against the inositol 1, 4, 5‐triphosphate receptor which is identical to the cerebellar Purkinje cell glycoprotein P₄₀₀ (P₄₀₀/IP₃R). In normal cerebellar Purkinje cells, the cell bodies, axons and dendrites including spiny branchlets were specifically stained by the antibody. By comparison, the immunoreactivity of the MD Purkinje cells ranged from negative to positive. The most frequent staining pattern in the MD Purkinje cells was that of cell bodies and proximal portions of the dendrites expressing P₄₀₀/IP₃R in varying degrees, with the peripheral dendrites including spiny branchlets not being stained. The Purkinje cells of the eight patients were also analyzed for expression of phosphorylated neurofilament proteins (pNFP), αB‐crystallin, stress‐response protein (srp) 72, srp 27 and ubiquitin. Most MD Purkinje cell bodies reacted with the antibody against pNFP. Although the proportion of stained Purkinje cells was less, a positive reaction was also observed with the antibodies to αB‐crystallin, srp 72 and srp 27. By contrast, no normal Purkinje cell was stained by these antibodies. Our results suggest that the function of P₄₀₀/IP₃R in the Purkinje cells of MD patients is impaired, that these cells have an aberrant phosphorylation of NFP and that some of the imparied Purkinje cells synthesize specific sets of stress‐related proteins.