Expression of Endogenous Retroviruses in Inbred Mice : Coordinate Regulation and Structure of Multiple Transcription Units

Year: 1985 DOI: 10.7907/165r-9v89
The control of expression of the murine antigen Gix and of other products of endogenous retroviruses, in strain 129 mice and in its congeneic partner strain 129 Gix⁻, is an example of the coordinate expression of a dispersed family of independent transcription units. In order to provide a molecular description of the Gix phenotype, evidence is presented, from DNA and RNA hybridization analyses using heterologous viral probes, indicating that this phenotype is specified by a distinct regulatory gene, defined genetically, that acts in trans to control the levels of accumulation of specific mRNA species. The steady state levels of several, structurally distinct polyadenylated RNA species are reduced in Gix⁻ mice, and a major reduction in transcription of these sequences accompanies this drop in abundance. Tissue specific patterns of accumulation of different sized RNA species were detected in numerous organs of the mouse, and the majority of these distinct transcripts were collectively regulated.

The isolation and characterization of cDNA copies of these endogenous retroviral transcripts demonstrated that they were derived from multiple, distinct transcription units. Differences among these RNA species were detected by S1 nuclease protection analyses , which confirmed the tissue specific patterns of RNA accumulation. The nucleotide sequences of endogenous virus cDNA clones fully documented the expression of distinct genes, the nature of the sequence heterogeneity, and the relationship of these normal cellular constituents to exogenous, infectious virus. The polymorphism was found to result from both single nucleotide changes and from deletions of different lengths of coding and non-coding information. Comparison of these sequences with exogenous virus demonstrated that the endogenous transcripts are closely related to the recombinant sequences of eukemogenic, mink cell focus forming viruses.