Evaluation of the silkworm <i>lemon</i> mutant as an invertebrate animal model for human sepiapterin reductase deficiency

Abstract

Human sepiapterin reductase (SR) deficiency is an inherited disease caused by <i>SPR</i> gene mutations and is a monoamine neurotransmitter disorder. Here, we investigated whether the silkworm <i>lemon</i> mutant could serve as a model of SR deficiency. A point mutation in the <i>BmSPR</i> gene led to a five amino acid deletion at the carboxyl terminus in the <i>lemon</i> mutant. In addition, classical phenotypes seen in SR deficient patients were observed in the <i>lemon</i> 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 <i>lemon</i> mutant. The silkworm <i>lemon</i> mutant also showed negative behavioural abilities. These results suggest that the silkworm <i>lemon</i> mutant has an appropriate genetic basis and meets the biochemical requirements to be a model of SR deficiency. Thus, the silkworm <i>lemon</i> 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.