Human sepiapterin reductase deficiency is an inherited disease caused by SPR gene mutations and is a monoamine neurotransmitter disorder. Here, we investigated whether the silkworm lemon mutant could serve as a model of sepiapterin reductase deficiency. A point mutation in the BmSPR gene led to a five amino acid deletion at the carboxyl terminus in the lemon mutant. In addition, classical phenotypes seen in sepiapterin reductase deficient patients were observed in the lemon mutant, including a normal phenylalanine level, a decreased dopamine and serotonin content, and an increased neopterin level. A recovery test showed that replenishment of L-dopa significantly increased the dopamine level in the lemon mutant. The silkworm lemon mutant also showed negative behavioral abilities. These results suggest that the silkworm lemon mutant has an appropriate genetic basis and meets the biochemical requirements to be a model of sepiapterin reductase deficiency. Thus, the silkworm lemon mutant can serve as a candidate animal model of sepiapterin reductase deficiency, which may be helpful in facilitating accurate diagnosis and effective treatment options of sepiapterin reductase deficiency.

The gene sequence and amino acid sequence used in the manuscript.