LoxP sites were inserted 5' and 3' of the keratin type II gene cluster, encompassing 0.68 Mb, 26 type II genes and 1 keratin type I gene (Krt18). Cre mediated recombination deleted the entire cluster leaving a single loxP site flanked by 3' and 5' hprt mini-genes and the the tyrosinase (Tyr) and agouti (A) coat color genes. The absence of the transcripts and gene products was confirmed by RT-PCR and immunofluorescence microscopy in homozygous embryos. Due to the absence of all type II keratins, all the type I keratins were sensitive to proteolysis, so homozygous mice lack all 54 keratin proteins. ES cells carrying Krt1ctm1Tmm and Igs11tm1Tmm and were used to create this deletion. (J:153804)