PB-Cre4+ApcL/L mice developed prostate hyperplasia with squamous metaplasia as early as 7 months of age26, and the penis of these mice was normal at 3.5 months of age but displayed mild dysplasia with hyperkeratosis at 12.5 months of age (Fig. 1d and Supplementary Fig. 1d). This evidence concerns the gene APC2 and Hyperkeratosis.