Selection for transgene homozygosity in embryonic stem cells results in extensive loss of heterozygosity

Embryonic stem cells offer unprecedented opportunities for random or target ed genome alterations in the mouse. We present here an efficient strategy t o create chromosome-specific loss of heterozygosity in embryonic stem cells . The combination of this method with genome-wide mutagenesis in ES cells ( using chemical mutagens or gene-trap vectors) opens up the possibility for in vitro or in vivo functional screening of recessive mutations in the mous e.