Fbxo4−/− or Fbxo4+/− mice spontaneously develop multiple tumors—including lymphoma, histiocytic sarcoma, and, less frequently, mammary and hepatocellular carcinomas [176]—as well as show an increased susceptibility to the N-nitrosomethylbenzylamine-induced development of papilloma [177]. This evidence concerns the gene FBXO4 and histiocytic sarcoma.