CYP17A1 is an enzyme in metabolism of steroids exhibiting 17alpha hydroxylase and C17-20 lyase activity. It is required for the synthesis of testosterone, estrogens, and cortisol by converting pregnenolone and progesterone to intermediate products. Recently, CYP17A1 gene was associated with coronary artery disease (CAD) and hypertension in genomewide association studies. A deficiency for this enzyme exists in humans and causes a rare form of congenital adrenal hyperplasia characterized by a dysfunctional sexual development in male patients, glucocorticoid lack, as well as a mineralocorticoid excess and according functional consequences (hypokalemia, hypertension). To investigate potential pathomechanisms that contribute to the development of CAD we generated Cyp17a1-deficient mice (Cyp17a1-/-) in the CardioGENE program. Breeding of heterozygous mice yielded offspring according to mendelian ratio. All Cyp17a1-/- littermates exhibited a female phenotype, but genotyping revealed that 55% of the offspring carried a Y-chromosome. Female Cyp17a1-/- mice had a higher body weight and increased subcutaneous as well as visceral fat deposits compared to female wild type littermates. Additionally, blood cholesterol levels were altered. Blood pressure and heart rate was measured in freely moving mice using telemetry. 24h mean arterial pressure (MAP) was similar in Cyp17a1-/- and wild type controls (~111 mmHg), whereas heart rate was slightly reduced in Cyp17a1-/- (591±5 vs. 620±12, P<0.05). In female wild type mice MAP was elevated at night (104±1 mmHg vs. 119±4 mmHg, day vs. night, P<0.01), as expected during enhanced activity. Similar findings were obtained in genotypic male (111±2 mmHg vs. 117±1 mmHg, P<0.05), but not in female Cyp17a1-/- mice (108±2 mmHg vs. 114±2 mmHg, P=0.08). Genotypic male Cyp17a1-/- (with female phenotype) had a significantly higher MAP than female wild type controls during day (111±2 vs. 104±1 mmHg, P<0.05). Serum potassium concentration was not different between genotypes. In a subgroup of mice voluntary running in a wheel was investigated, in which wild type mice ran up to 6 km/night. Interestingly, Cyp17a1-/- ran less distance (only 25%) but lost approximately 10% of their body weight during this period of 10 d, while weight did not decrease in wild type mice. We conclude that Cyp17a1 has a strong impact on body weight and fat deposition. Its role in blood pressure regulation is less obvious, which is also reflected by the normokalemia suggesting that aldosterone is not produced in excess as observed in humans. It remains to be determined whether the alterations in cholesterol levels enhance atherosclerosis and CAD in these mice or whether obesity itself is the only contributing factor.