Stability of transgene methylation patterns in mice: position effects, strain specificity and cellular mosaicism.
The methylation status of a transgene, which carried the adenovirus type 2 E2A late promoter linked to the chloramphenicol acetyltransferase gene, was studied in three transgenic mouse lines (5-8, 7-1 and 8-1). These lines were analysed over a large number of offspring generations beyond the founder animal. In mating experiments, the influence of the parent-of-origin and strain-specific backgrounds on the transgene methylation patterns were assessed and found to have no effect on the pre-established methylation patterns in mouse lines 5-8 and 8-1. The founder animal 7-1 carried two groups of a total of ten transgenes, which were located on two different chromosomes. These arrays of transgenes could be segregated into separate mouse lines 7-1A and 7-1B. The transgenes of 7-1A animals exhibited cellular mosaic methylation patterns that were demethylated in approximately 10% of the offspring in a mixed genetic background. Upon further transmission of these transgenes in a mixed genetic background, the grandparental methylation patterns were reestablished in most progeny. Mating to inbred DBA/2 mice resulted in maintenance of the demethylated pattern or in further demethylation of the transgenes in approximately 50% of the offspring. In contrast, an equal number of transgenic siblings from matings to C57BL/6 mice showed a return to the original methylation pattern. The mosaic methylation status of this locus was apparently controlled by mouse-strain-specific factors. The methylation patterns of the 7-1B transgenes were not cellular mosaic and remained stable in all offspring, as with lines 5-8 and 8-1. Hence, the strain-dependent and cellular mosaic transgene methylation patterns of 7-1A animals were probably a consequence of the chromosomal integration site of the transgenes (position effect).
Koetsier
P A
PA
Institut für Genetik, Universität zu Köln, Germany.
Mangel
L
L
Schmitz
B
B
Doerfler
W
W
D000256:Adenoviridae / Q000235:genetics; D017502:Adenovirus E2 Proteins / Q000235:genetics; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D005798:Genes, Bacterial; D005814:Genes, Viral; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009030:Mosaicism; D009928:Organ Specificity; D010375:Pedigree; D011401:Promoter Regions, Genetic; D013045:Species Specificity
D017502:Adenovirus E2 Proteins; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase