Immunohistochemical localization and distribution of torsinA in normal human and rat brain

Dystonia is a disease of basal ganglia function, the pathophysiology of whi ch is poorly understood. Primary torsion dystonia is one of the most severe types of inherited dystonia and can be transmitted in an autosomal dominan t manner. Recently, one mutation causing this disorder was localized to a g ene on chromosome 9q34, designated DYT1, which encodes for a novel protein termed torsinA. The role of this protein in cellular function, in either no rmal or dystonic individuals is not known. We have developed a polyclonal a ntibody to torsinA and report its localization and distribution in normal h uman and rat brain. We demonstrate that torsinA is widely expressed in brai n and peripheral tissues. Immunohistochemical studies of normal human and r at brain reveal the presence of torsinA in the dopaminergic neurons of the substantia nigra pars compacta (SNc), in addition to many other regions, in cluding neocortex, hippocampus, and cerebellum. Labeling is restricted to n eurons, as shown by double-immunofluorescence microscopy, and is present in both nuclei and cytoplasm. An ATP-binding property for torsinA has been su ggested by its homology to ATP-binding proteins; this was confirmed by enri chment of torsinA in ATP-agarose affinity-purified fractions from tissue ho mogenates. An understanding of the role of torsinA in cellular function and the impact of the mutation (deletion of a glutamic acid at residue 303) is Likely to provide insights into the etiopathogenesis of primary dystonia. (C) 2000 Elsevier Science B.V. All rights reserved.