Complex patterns of inheritance of an imprinted murine transgene suggest incomplete germline erasure

Here we report a transgenic mouse line that exhibits significant deviations from a classic pattern of parental imprinting. When the transgene is passe d through the female germline, it is completely silenced in some offspring while in others expression is reduced, This variable expressivity does not appear to be the result of differences in the presence of unlinked modifier s. Female transmission of the transgene is associated with hypermethylation , The transgene is generally reactivated on passage through the male germli ne, Extended pedigrees reveal complex patterns of inheritance of the phenot ype, The most likely explanation for this result is that the imprint is not completely erased and reset when passed through the germline of either sex . FISH analysis reveals that the transgene has integrated into chromosome 3 band E3, a region not known to carry imprinted genes, and the integration site shows no sign of allele-specific differential methylation, These findi ngs, in conjunction with other recent work, raise the possibility that the introduction of foreign DMA into the mammalian genome, either through retro transposition or transgenesis, may be associated with parental imprinting t hat is not always erased and reset during meiosis.