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This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH 4 )-deficient  Spr   −/−  mice by the dietary supplementation of tyrosine. Since BH 4  is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH 4 -deficient  Spr   −/−  mice. We found that  Spr   −/−  mice display variable ‘open-field’ behaviors, impaired motor functions on the ‘rotating rod’, and dystonic ‘hind-limb clasping’. In this study, we report that these aberrant motor deficits displayed by  Spr   −/−  mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of  Spr   −/−  mice may not be the biological feature of aberrant motor behaviors associated with BH 4  deficiency. Brain levels of dopamine (DA) and its metabolites in  Spr   −/−  mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of  Spr   −/−  mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH 4 -deficiency.

Amelioration of Behavioral Abnormalities in BH4-deficient Mice by Dietary Supplementation of Tyrosine