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In order to identify molecular markers of prion disease in peripheral tissues, we used the differential display reverse-transcriptase polymerase chain reaction (DDRT-PCR) procedure to compare gene expression in spleens of infected and uninfected mice. In this study, we identified a novel erythroid-specific gene that was differentially expressed as a result of prion infection. We were able to demonstrate that a decrease in the expression levels of this transcript in hematopoietic tissues was a common feature of prion diseases. Our findings suggest a previously unknown role for the blood erythroid lineage in the development of prion diseases and should provide a new focus for research into diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]