Transposition of intracisternal A-particle genes in mouse hybridomas

Abstract

A nonfunctional immunoglobulin kappa-chain gene previously shown to contain intracisternal A-particle (IAP) sequences within one of its introns was further characterized by DNA and RNA blot analysis. The results of these experiments indicate that the joining of the IAP sequences to the kappa-chain gene was a consequence of an insertion event which presumably involved a complete IAP gene. It is postulated that the insertion of the IAP gene has altered the secondary or tertiary structure of the kappa-chain pre-mRNA, resulting in the utilization of a "cryptic" 5' splice site. The detection of numerous IAPs in isogenous wild-type hybridoma cells by electron microscopy suggests that transposition of IAP genes might proceed via the reverse transcription of IAP-associated RNA. These findings raise the possibility that transposition of IAP genes might also occur in other IAP-positive mouse cells. In particular, insertional mutagenesis by IAP genes in IAP-producing tumor cells could play a role in tumor cell heterogeneity or tumor progression. We have also investigated the possibility that IAP-related sequences might be present in the human genome. Using nonstringent hybridization conditions, multiple discrete restriction fragments could be detected in human DNA with several mouse IAP-specific probes.