Preimplantation lethality of monosomy for mouse chromosome 19.

Abstract

IT remains a mystery why autosomal trisomy is found more frequently than autosomal monosomy in man. Several surveys of spontaneous abortions have revealed these chromosomal abnormalities in proportions of 26% (ref. 1) and 0.1% (refs 1, 2), respectively, while a prospective study of 47,000 newborn babies revealed no full monosomy and only five cases in which parts of chromosomes were missing3. Similarly, in mouse embryos from translocation stocks bred to produce aneuploid progeny, high frequencies of trisomy but no monosomy are found after 12–13 days4,5. This is hard to understand because most autosomal aneuploidy is assumed to result from meiotic nondisjunction, so that for every gamete carrying two copies of a particular chromosome there should be a complementary gamete carrying none. However, the deficiency of monosomic embryos could be because nullisomic gametes are less able than disomic gametes to participate in fertilisation, or because the resulting monosomic embryos are less viable early in gestation. We report here the investigation of these possibilities in a mouse system which is known to produce a high frequency of nondisjunction. Equal numbers of monosomic and trisomie progeny were found early in gestation, but while some monosomies were compatible with survival to implantation, monosomy for the smallest mouse autosome, chromosome 19, was lethal at the early to mid-blastocyst stage. This lethality did not seem to be the result of the expression of recessive lethal genes.