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This Article Full Text Full Text (PDF) [Supplemental Data] All Versions of this Article: 76/2/286    most recent biolreprod.106.056739v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ideraabdullah, F. Y. Articles by Villena, F. P.-M. d. Search for Related Content PubMed PubMed Citation Articles by Ideraabdullah, F. Y. Articles by Villena, F. P.-M. d. Agricola Articles by Ideraabdullah, F. Y. Articles by Villena, F. P.-M. d.

Rescue of the Mouse DDK Syndrome by Parent-of-Origin-Dependent Modifiers¹

Department of Genetics,³ Curriculum in Genetics and Molecular Biology,⁴ Departments of Nutrition,⁵ and Cell and Molecular Physiology,⁶ Carolina Center for Genome Sciences,⁷ Lineberger Comprehensive Cancer Center,⁸ University of North Carolina, Chapel Hill, North Carolina 27599-7264 Genetics Division,⁹ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

ABSTRACT

When females of the DDK inbred mouse strain are mated to males of other strains, 90–100% of the resulting embryos die during early embryonic development. This DDK syndrome lethality results from incompatibility between an ooplasmic DDK factor and a non-DDK paternal gene, which map to closely linked loci on chromosome 11. It has been proposed that the expression of the gene that encodes the ooplasmic factor is subject to allelic exclusion in oocytes. Previous studies have demonstrated the existence of recessive modifiers that increase lethality in the C57BL/6 and BALB/c strains. These modifiers are thought to skew the choice of allele undergoing allelic exclusion in the oocytes of heterozygous females. In the present study, we demonstrate the presence of modifiers in three Mus musculus domesticus wild-derived strains, PERA, PERC, and RBA. These modifiers completely rescued DDK syndrome lethality. We mapped the major locus that is responsible for rescue in PERA and PERC crosses to proximal chromosome 13 and named this locus Rmod1 (Rescue Modifier of the DDK Syndrome 1). Our experiments demonstrate that PERA or PERC alleles at Rmod1 rescue lethality independently of allelic exclusion. In addition, rescue of the lethal phenotype depends on the parental origin of the Rmod1 alleles; transmission through the dam leads to rescue, while transmission through the sire has no effect.

developmental biology, early development, embryo, oocyte, ovum

¹Supported in part by grants from the National Science Foundation (MCB-0133526 to F.P-M.V.) and the National Institutes of Health (U01HD43430 to D.R.B.).

Correspondence: ²Fernando Pardo-Manuel de Villena, Department of Genetics, CB#7264, 103 Mason Farm Road, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599-7264. FAX: 919 966 3630; e-mail: Fernando{at}med.unc.edu