Pms2^tm2(cre)Lisk

The SV40 nuclear localization signal (NLS) within the cre sequence was modified to contain an 12-base pair A-T run which preserved the NLS, but added an extra A inducing a +1 bp shift. An IRES was cloned 5' to the cre ATG signal with a neo cassette cloned 3' to the recombinase sequence. The IRES-cre-neo vector was used for homologous recombination in ES cells, resulting in the IRES-cre inserting into the Pms2 locus replacing exon 2. The extra A in the NLS causes the cre to be out of frame (inactive). Because this Pms2 allele is null (thus deficient in DNA mismatch repair), homozygotes will have an increased frequency of -1 bp resulting in cre reversion and thus in cre expression. (J:204653)