That reduced levels of Nkx3.1 itself are not responsible for the morphological changes diagnostic of high grade PIN is evidenced by the findings that Nkx3.1(−/−) knockout mice [52], [53], [54], or mice with targeted disruption of Nkx3.1 alleles in adulthood [66], show only very subtle changes such as hyperplasia and mild dysplasia (PIN-like), and even these are clearly much less pronounced that that seen in the Lo-MYC and Hi-MYC mice. This evidence concerns the gene MYC and prostate intraepithelial neoplasia.