Kras^tm2Tyj

Insertion of the targeting vector results in a duplication of exon 1 with a neomycin resistance gene cassette between the duplicate exons. The upstream (inserted) exon 1 contains an activating glycine to aspartic acid mutation at codon 12 (p.G12D). In the absence of intrachromosomal recombination, this allele does not produce any protein and mutant homozygotes die during embryogenesis. In heterozygotes, when intrachromosomal recombination occurs in vivo, half of the recombination events produce an active mutant allele coding for the p.G12D amino acid substitution and half produce a wild-type allele. Expression of G12D protein results in the formation of lung tumors and death at ~300 days (10 months). (J:68981)