A targeting construct consisting of an IRES-PLAP-IRES-lacZ (IRES, internal ribosomal entry site; PLAP, placental alkaline phosphatase and lacZ has a nuclear localization signal) sequence and a self-excising neo resistance cassette (ACN) was used to target the Pgr locus in ES cells. ES cell were injected into blastocysts to produce chimeras. The neo gene in the ACN cassette is self-excised during passage through the male germline so F1 progeny from crosses of chimeric males to wild-type C57BL/6J females had ACN deletion.