Effects of the C.886C>T Mutation in the Mouse Tyrosine Hydroxylase Gene on Behavior and Dopamine System of the Brain

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Ismail Alsalloum^1,2, Ilya A. Rakhov^1,2, Polina D. Komleva², Valentina N. Kuranova³, Anastasia E. Bastrikova³, Alexander V. Kulikov², and Darya V. Bazovkina^2,a*

¹Novosibirsk State University, 630090 Novosibirsk, Russia

²Federal Research Center, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

³National Research Tomsk State University, 634050 Tomsk, Russia

^* To whom correspondence should be addressed.

Received: January 20, 2026; Revised: April 29, 2026; Accepted: May 18, 2026

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Dopamine (DA) is a critical regulator of physiological functions and adaptive behavior. The enzyme tyrosine hydroxylase (TH) catalyzes hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (DOPA), which is the first and rate-limiting step in the DA biosynthesis. Mutations in the human TH gene have been linked to dystonia, catalepsy, and catatonia. In the present study, we examined how the functional mutation c.886C>T in the Th gene affects the brain DA system and behavior in mice. The C allele – which confers high TH enzyme activity – was introgressed from the Mus musculus castaneus subspecies into the C57BL/6 inbred background, yielding three congenic genotypes: B6-886CC, B6-886CT, and B6-886TT. Males of each genotype were evaluated in a battery of behavioral tests; and TH activity, levels of DA and DA metabolites, norepinephrine, and mRNA levels of the key DA system genes were measured across the brain structures. The three genotypes did not differ in body weight, locomotor activity, motor coordination, or cognitive performance. However, the B6-886TT mice showed significantly reduced exploratory activity in the open field test relative to the B6-886CC and B6-886CT animals. The B6-886TT mice also exhibited lower TH activity and DA content in the midbrain, and reduced DOPAC levels in the hypothalamus, compared to the B6-886CC animals. The c.886C>T mutation had no detectable effect on expression of the genes encoding key DA metabolic enzymes or DA receptors. In a separate experiment, we genotyped 80 DNA samples from the Mus musculus collected across natural populations in Russia. The C and T allele frequencies were 0.981 and 0.019, respectively, suggesting that the T allele may be subject to negative natural selection.

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KEY WORDS: tyrosine hydroxylase, dopamine, brain, gene expression, behavior, mice

DOI: 10.1134/S0006297926600171

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