Evaluation of the silkworm mutant as an invertebrate animal model for human sepiapterin reductase deficiency.

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