A POSTTRANSCRIPTIONAL REGULATORY MECHANISM RESTRICTS EXPRESSION OF THE PARANEOPLASTIC CEREBELLAR DEGENERATION ANTIGEN CDR2 TO IMMUNE PRIVILEGED TISSUES

Paraneoplastic cerebellar degeneration (PCD) is believed to be an auto immune disorder initiated by the ectopic expression of a neuron-specif ic protein in breast and ovarian tumors. PCD antisera was used previou sly to identify several cerebellar degeneration-related (cdr) genes en coding putative PCD antigens. We have found that the cdr2 gene, which encodes a cytoplasmic leucine zipper protein of unknown function, is e xpressed in PCD-associated tumors, whereas other cdr genes are not; th us, cdr2 encodes the PCD tumor antigen. To determine whether the expre ssion pattern of cdr2 is consistent with its proposed role in PCD, we have isolated the mouse homolog and examined both the mRNA and protein distribution in adult tissues. We have found that cdr2 mRNA is expres sed in almost all tissues, whereas the protein is expressed only in th e brain and testis. Within the brain, both the cdr2 mRNA and immunorea ctivity are confined primarily to neurons in the cerebellum and brains tem, the regions most affected in PCD. These results suggest first tha t the tissue-specific expression of cdr2 is regulated al a post-transc riptional level. Moreover, because the brain and testis are considered to be immune-privileged sites, the expression pattern of cdr2 is comp atible with the autoimmune model of PCD pathogenesis.