セピアプテリン還元酵素遺伝子破壊マウスは高度な持続勃起症（Priapism）を発症する。

抄録

(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for phenylalanine-catabolism, and production of monoamines and nitric oxide (NO). Sepiapterin reductase (SPR) catalysis the final step of BH4 biosynthesis. Previously, we established SPR gene disrupted (Spr^-/-) mice (OYC32, Lexicon Pharmaceuticals Inc.) and reported that they exhibited dystonic posture, low body weight, hyperphenylalaninemia and unstable hypertension with bradycardia. Recently, we found that Spr^-/- mice suffered from severe priapism (persistent erection) at high incidence (69.2%) and analyzed their penile tissues to reveal the mechanism. The content of BH4 and noradrenaline in the penile homogenate of Spr^-/- mice significantly decreased compared to those of wild type (Spr^+/+) mice, which were 0.69% and 17.4%, respectively. There was no significant difference in the protein amount of eNOS, PDE5A, p-PDE5A between two genotypes. Tyrosine hydroxylase significantly decreased and, on the contrary, that of nNOS significantly increased in the penis of Spr^-/- mice. NO metabolites significantly increased in the penis of Spr^-/- also. Thus, we concluded that sympathetic nerve failure and up-regulation of NO production contribute to the severe priapism of Spr^-/- mice.