The development of monosomy 19 mouse embryos

Abstract

In general, autosomal monosomy is lethal much earlier in mammalian development than autosomal trisomy. In an attempt to understand why monosomy is so deleterious, we have begun to characterize the development of mouse embryos monosomic for chromosome 19. A dramatic loss of monosomy 19 embryos was found to occur between days 3 and 4 of development. This loss occurred both in vivo and in vitro and with intact blastocysts or isolated inner cell masses. Experiments with inbred strains showed that this loss was not due to the expression of recessive lethal genes. While monosomic embryos were found to have fewer cells than normal and trisomic litter-mates beginning at the early morula stage, the ability to form blastocysts is not interfered with. Electron microscopy revealed no difference in the cellular ultrastructure of monosomic when compared with diploid embryos. Furthermore, two-dimensional gel electrophoresis did not reveal any differences in the proteins synthesized by monosomic, trisomic or diploid litter-mates when examined at day 3 of development. These results indicate a lack of gross genomic disturbances in monosomic embryos. When monosomy in equilibrium diploid chimaeras were made, viable monosomic cells were found in day-9 post-implantation embryos, well past the lethal period. Thus, in chimaeric embryos, the normal cells appear to be able to provide whatever is lacking, suggesting that monosomy 19 is not a cell lethal. Instead, death may be due to a dosage alteration in specific gene products needed during early development.