Submitted August 23, 2006
Returned for revision September 27, 2006
Accepted October 12, 2006
Embryo
Rescue of the Mouse DDK Syndrome by Parent-of-Origin
Dependent Modifiers
Folami Y. Ideraabdullah ,
Kuikwon Kim ,
Daniel Pomp ,
Jennifer L. Moran ,
David Beier ,
and
Fernando Pardo-Manuel de Villena *
* To whom correspondence should be addressed. E-mail: fernando{at}med.unc.edu.
Abstract
When females of the DDK inbred mouse strain are mated to
males of many other strains, 90-100% of the resulting
embryos die during early embryonic development. This "DDK
syndrome" lethality results from an incompatibility
between an ooplasmic DDK factor and a non-DDK paternal
gene, both of which map to closely linked loci on
chromosome 11. It has been proposed that expression of the
gene encoding the ooplasmic factor is subject to allelic
exclusion in oocytes. Previous studies demonstrated the
existence of recessive modifiers in the C57BL/6 and BALB/c
strains that increase lethality. These modifiers are
thought to skew the choice of allele undergoing allelic
exclusion in the oocytes of heterozygous females. Here, we
demonstrate the presence of modifiers in three Mus
musculus domesticus wild-derived strains, PERA, PERC,
and RBA. These modifiers completely rescue the DDK
syndrome lethality. We have mapped the major locus
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.
Key words:
Embryo •
Developmental biology •
Early development •
Oocyte development •
Ovum
