Exon 1 of Npr2 was replaced with an nls-lacZ (nuclear localization sequence-lacZ) expression cassette and polyadenylation sequence by homologous recombination in ES cells. The targeting vector also contained a self-excising cre recombinase-neo cassette (cre is expressed from a testis-specific promoter, so the neo is deleted in the male germline). No Npr2 protein was detected in samples from homozygotes.