The mouse intracisternal A particle (IAP) genes are a family of moderately repetitive sequences containing about 1,000 copies per haploid genome of Mus musculus. They are largely made of two size classes: 7 kb and 4 kb in length flanked at both the 5' end and the 3' end of the gene by an additional 400 bp of long terminal repeat (LTR) sequences. These genes are endogenous retroviral-like. They are expressed in early development, up to the 8-cell stage, and in many forms of mouse tumors but are not expressed in tissues of young adults. We have recently found that IAP genes are fully methylated in all non-transcribed tissues, but demethylated in tumors where they are actively transcribed. Rearrangement of IAP genes in mouse liver occurs throughout the life span of the animal, beginning early in development and continuing into senescense. Taking cloned IAP sequences as a hybridization probe, we have found that the 4 kb class of IAP genes is also conserved in Syrian hamster in rat and in man. In addition, we have observed that the long terminal repeat (LTR) DNA are associated not only with the coding sequences of IAP genes, they also appear separately within another repetitive gene family (the 1.35 kb Eco RI satellite DNA (SAT)) in the genomes of mouse, Syrian hamster, rat and man. In view of the possible involvement of endogenous viral expression in many human aging diseases, the present study is initiated in order to test whether activation and modification of IAP genes occur during sensescence. Two model systems, mouse and Syrian hamster, are used for this investigation. All methods described in this proposal have been previously tested.
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