Multiple transcripts of the human Cu,Zn superoxide dismutase gene

We have identified five alternatively spliced transcripts of the gene for h uman Cu,Zn superoxide dismutase (SOD1), a causative gene for autosomal domi nant amyotrophic lateral sclerosis (ALS). The splice variants of wild-type or mutant SOD1 were expressed in a tissue-specific manner; therefore, their expression may be regulated to modify SOD1 function. In addition, the expr ession in the brain implies that variants may play a role in the nervous sy stem, the region involved in ALS. Immunoblot study of HeLa cells transfecte d with two variants encoding C-terminal truncated proteins did not show the proteins of expected size. However, this observation is consistent with th e previous study of C-terminal truncated mutant proteins that cause ALS, su ggesting that both variant and mutant proteins may share certain properties , such as instability or insolubility in the cytosol. These findings sugges t that the splice variants may contribute to a physiological function of SO D1 or to a pathological mechanism in ALS. (C) 2000 Academic Press.