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Nucleic Acids Research, 2000, Vol. 28, No. 17 3301-3309
© 2000 Oxford University Press

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

Margot Kearns, Jost Preis, Margaret McDonald1, Christine Morris1 and Emma Whitelaw*

Department of Biochemistry, University of Sydney, NSW 2006, Australia and 1Cytogenetic and Molecular Oncology Unit, Department of Pathology, Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand

Here we report a transgenic mouse line that exhibits significant deviations from a classic pattern of parental imprinting. When the transgene is passed 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 modifiers. Female transmission of the transgene is associated with hypermethylation. The transgene is generally reactivated on passage through the male germline. Extended pedigrees reveal complex patterns of inheritance of the phenotype. 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 findings, in conjunction with other recent work, raise the possibility that the introduction of foreign DNA into the mammalian genome, either through retrotransposition or transgenesis, may be associated with parental imprinting that is not always erased and reset during meiosis.

* To whom correspondence should be addressed. Tel: +61 2 9351 2549; Fax: +61 2 9351 4726; Email: e.whitelaw@biochem.usyd.edu.au


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