So far, all attempts to generate a ccRCC mouse model that phenocopies the hallmarks of ccRCC, i.e. the clear cell histology associated with perturbed metabolic control in combination with metastatic potential has proven difficult; Mice homozygous for the Vhl null allele die in utero because of vascular abnormalities of the placenta57, while Vhl+/− mice52 or mice in which Vhl was mosaically deleted with a human β-actin driven Cre58, did not display any signs of renal pathology. The gene discussed is ACTB; the disease is nonpapillary renal cell carcinoma.