Powering mammalian genetic screens with mouse haploid embryonic stem cells

Generating homozygous mutants in mammalian cells has been complicated by their diploid genome. If one allele of an autosomal gene was disrupted, the resulting heterozygous mutant is unlikely to display a phenotype due to the existence of the other allele. Although embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are excellent cellular models for analyzing developmental events or disease phenotypes in vitro, a direct analysis of recessive phenotypes has been limited by their diploidy. Recently, four independent research groups reported successful derivation of haploid mouse embryonic stem cells which provide an effective platform for studying mammalian gene function. The aim of this review is to describe the strategies for deriving haploid ESCs and compare their characteristics with diploid ESCs, and further discuss the potential application of haploid ESCs in genetic screening and homozygous mutant animal production.