A targeting vector was generated to insert an improved IRES2i site, a humanized cre open reading frame and an FRT-flanked neo selection cassette into exon 12 of histidine decarboxylase between the stop codon and polyadenylation sequence, by homologous recombination in ES cells. Chimeras were produced by ES cell injection into C57BL/6J blastocysts. The resulting line was bred with Flp deleter mice to remove the neo cassette.