We developed transgenic mice with a gain-of-function <i>Epas1<sup>A529V</sup></i> mutation (corresponding to human <i>EPAS1<sup>A530V</sup></i>), which demonstrated elevated levels of erythropoietin and polycythemia, a decreased urinary metanephrine-to-normetanephrine ratio, and increased expression of somatostatin in the ampullary region of duodenum.