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The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain. / Alsalloum, Ismail; Moskaliuk, Vitalii S.; Rakhov, Ilya A. et al.

In: Biochemistry (Moscow), Vol. 89, No. 6, 06.2024, p. 1024-1030.

Research output: Contribution to journal › Article › peer-review

Harvard

Alsalloum, I, Moskaliuk, VS, Rakhov, IA, Bazovkina, DV & Kulikov, AV 2024, 'The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain', Biochemistry (Moscow), vol. 89, no. 6, pp. 1024-1030. https://doi.org/10.1134/S000629792406004X

APA

Alsalloum, I., Moskaliuk, V. S., Rakhov, I. A., Bazovkina, D. V., & Kulikov, A. V. (2024). The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain. Biochemistry (Moscow), 89(6), 1024-1030. https://doi.org/10.1134/S000629792406004X

Vancouver

Alsalloum I, Moskaliuk VS, Rakhov IA, Bazovkina DV, Kulikov AV. The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain. Biochemistry (Moscow). 2024 Jun;89(6):1024-1030. doi: 10.1134/S000629792406004X

Author

Alsalloum, Ismail ; Moskaliuk, Vitalii S. ; Rakhov, Ilya A. et al. / The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain. In: Biochemistry (Moscow). 2024 ; Vol. 89, No. 6. pp. 1024-1030.

BibTeX

@article{134610cf2dcc4e9aaf96805053cb7a70,
title = "The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain",
abstract = "Abstract: Tyrosine hydroxylase (TH) catalyzes hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine, the initial and rate-limiting step in the synthesis of dopamine, noradrenaline, and adrenaline. Mutations in the human TH gene are associated with hereditary motor disorders. The common C886T mutation identified in the mouse Th gene results in the R278H substitution in the enzyme molecule. We investigated the impact of this mutation on the TH activity in the mouse midbrain. The TH activity in the midbrain of Mus musculus castaneus (CAST) mice homozygous for the 886C allele was higher compared to C57BL/6 and DBA/2 mice homozygous for the 886T allele. Notably, this difference in the enzyme activity was not associated with changes in the Th gene mRNA levels and TH protein content. Analysis of the TH activity in the midbrain in mice from the F2 population obtained by crossbreeding of C57BL/6 and CAST mice revealed that the 886C allele is associated with a high TH activity. Moreover, this allele showed complete dominance over the 886T allele. However, the C886T mutation did not affect the levels of TH protein in the midbrain. These findings demonstrate that the C886T mutation is a major genetic factor determining the activity of TH in the midbrain of common laboratory mouse strains. Moreover, it represents the first common spontaneous mutation in the mouse Th gene whose influence on the enzyme activity has been demonstrated. These results will help to understand the role of TH in the development of adaptive and pathological behavior, elucidate molecular mechanisms regulating the activity of TH, and explore pharmacological agents for modulating its function.",
keywords = "C886T mutation, activity, brain, expression, mice, tyrosine hydroxylase",
author = "Ismail Alsalloum and Moskaliuk, {Vitalii S.} and Rakhov, {Ilya A.} and Bazovkina, {Daria V.} and Kulikov, {Alexander V.}",
year = "2024",
month = jun,
doi = "10.1134/S000629792406004X",
language = "English",
volume = "89",
pages = "1024--1030",
journal = "Biochemistry (Moscow)",
issn = "0006-2979",
publisher = "Maik Nauka-Interperiodica Publishing",
number = "6",

}

RIS

TY - JOUR

T1 - The C886T Mutation in the Th Gene Reduces the Activity of Tyrosine Hydroxylase in the Mouse Brain

AU - Alsalloum, Ismail

AU - Moskaliuk, Vitalii S.

AU - Rakhov, Ilya A.

AU - Bazovkina, Daria V.

AU - Kulikov, Alexander V.

PY - 2024/6

Y1 - 2024/6

N2 - Abstract: Tyrosine hydroxylase (TH) catalyzes hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine, the initial and rate-limiting step in the synthesis of dopamine, noradrenaline, and adrenaline. Mutations in the human TH gene are associated with hereditary motor disorders. The common C886T mutation identified in the mouse Th gene results in the R278H substitution in the enzyme molecule. We investigated the impact of this mutation on the TH activity in the mouse midbrain. The TH activity in the midbrain of Mus musculus castaneus (CAST) mice homozygous for the 886C allele was higher compared to C57BL/6 and DBA/2 mice homozygous for the 886T allele. Notably, this difference in the enzyme activity was not associated with changes in the Th gene mRNA levels and TH protein content. Analysis of the TH activity in the midbrain in mice from the F2 population obtained by crossbreeding of C57BL/6 and CAST mice revealed that the 886C allele is associated with a high TH activity. Moreover, this allele showed complete dominance over the 886T allele. However, the C886T mutation did not affect the levels of TH protein in the midbrain. These findings demonstrate that the C886T mutation is a major genetic factor determining the activity of TH in the midbrain of common laboratory mouse strains. Moreover, it represents the first common spontaneous mutation in the mouse Th gene whose influence on the enzyme activity has been demonstrated. These results will help to understand the role of TH in the development of adaptive and pathological behavior, elucidate molecular mechanisms regulating the activity of TH, and explore pharmacological agents for modulating its function.

AB - Abstract: Tyrosine hydroxylase (TH) catalyzes hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine, the initial and rate-limiting step in the synthesis of dopamine, noradrenaline, and adrenaline. Mutations in the human TH gene are associated with hereditary motor disorders. The common C886T mutation identified in the mouse Th gene results in the R278H substitution in the enzyme molecule. We investigated the impact of this mutation on the TH activity in the mouse midbrain. The TH activity in the midbrain of Mus musculus castaneus (CAST) mice homozygous for the 886C allele was higher compared to C57BL/6 and DBA/2 mice homozygous for the 886T allele. Notably, this difference in the enzyme activity was not associated with changes in the Th gene mRNA levels and TH protein content. Analysis of the TH activity in the midbrain in mice from the F2 population obtained by crossbreeding of C57BL/6 and CAST mice revealed that the 886C allele is associated with a high TH activity. Moreover, this allele showed complete dominance over the 886T allele. However, the C886T mutation did not affect the levels of TH protein in the midbrain. These findings demonstrate that the C886T mutation is a major genetic factor determining the activity of TH in the midbrain of common laboratory mouse strains. Moreover, it represents the first common spontaneous mutation in the mouse Th gene whose influence on the enzyme activity has been demonstrated. These results will help to understand the role of TH in the development of adaptive and pathological behavior, elucidate molecular mechanisms regulating the activity of TH, and explore pharmacological agents for modulating its function.

KW - C886T mutation

KW - activity

KW - brain

KW - expression

KW - mice

KW - tyrosine hydroxylase

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85197908112&origin=inward&txGid=1db945adb7ae7454bd3ceaa382afc526

UR - https://www.mendeley.com/catalogue/96f72b98-3cab-383a-ace1-e2184e4ad074/

U2 - 10.1134/S000629792406004X

DO - 10.1134/S000629792406004X

M3 - Article

C2 - 38981698

VL - 89

SP - 1024

EP - 1030

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 6

ER -

ID: 61118589