ETn insertion in the mouse Adcy1 gene: transcriptional and phylogenetic analyses

Early retrotransposons (ETn) are murine transposable elements, bearing some structural similarity to integrated proviruses, and can be insertional mut agens. We have recently identified the causative mutation of the barrelless (Adcy1(brl)) phenotype as an integration of a 5.7-kb ETn in an intron of t he adenylyl cyclase type I (Adcy1) gene. In the present study, Northern blo t analysis shows that the ETn insertion results in loss of the normal Adcy1 transcript, a finding consistent with the loss-of-function Adcy1(brl) muta tion, and generation of shorter transcripts. These aberrant transcripts are the products of abnormal RNA splicing and termination owing to the inserte d sequence, and transcription initiation within the 3' long terminal repeat (LTR) of the ETn. The DNA sequences of the LTRs were compared in phylogene tic analyses with LTRs from 22 other ETn-related sequences. Three distinct families of ETn sequences can be identified on the basis of their LTRs. The ETn found in Adcy1(brl) is a member of a family that includes all classifi ed ETn elements known to have recently transposed. Further, of the four kno wn solitary (solo) LTRs, we have identified two that show evidence of recom bination between LTRs from different ETn families.