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 mutagens. We have recently identified the causative mutation of the barrelless (Adcy1brl) phenotype as an integration of a 5.7-kb ETn in an intron of the adenylyl cyclase type I (Adcy1) gene. In the present study, Northern blot analysis shows that the ETn insertion results in loss of the normal Adcy1 transcript, a finding consistent with the loss-of-function Adcy1brl mutation, and generation of shorter transcripts. These aberrant transcripts are the products of abnormal RNA splicing and termination owing to the inserted sequence, and transcription initiation within the 3' long terminal repeat (LTR) of the ETn. The DNA sequences of the LTRs were compared in phylogenetic 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 Adcy1brl is a member of a family that includes all classified ETn elements known to have recently transposed. Further, of the four known solitary (solo) LTRs, we have identified two that show evidence of recombination between LTRs from different ETn families.
Leong
W L
WL
Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Dobson
M J
MJ
Logsdon
J M
JM
Abdel-Majid
R M
RM
Schalkwyk
L C
LC
Guernsey
D L
DL
Neumann
P E
PE
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D018626:Retroelements; D012689:Sequence Homology, Nucleic Acid
D012333:RNA, Messenger; D018626:Retroelements; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1