To define the role, if any, of HIF activation in FH-associated neoplasia, we combined inactivation of Fh1 with Hif-1α, Hif-2α, or both Hif-α isoforms, measured the frequency of renal cyst formation in a mouse model recapitulating the cystic phenotype of the human disease, and compared the outcome with that of genetic inactivation of the Hif prolyl hydroxylases (Phds). Here, HIF1A is linked to Renal cyst.