A brain-specific decrease of the tyrosine hydroxylase protein in sepiapterin reductase-null mice-as a mouse model for Parkinson's disease

Chisato Takazawa, Kengo Fujimoto, Daigo Homma, Chiho Ichinose, Takahide Nomura, Hiroshi Ichinose, Setsuko Katoh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Sepiapterin reductase (SPR) is an enzyme that acts in the third and final step of tetrahydrobiopterin (BH4) biosynthesis. The human Spr gene locates within the region of 2.5 MB mapped to PARK3, an autosomal dominant form of familial Parkinson's diseases. In order to explore the role of SPR in the metabolism of BH4, we produced and analyzed Spr-deficient mice. Most of Spr-null mice survived beyond two weeks. Whereas the BH4 contents in the homozygous mutant mice were greatly decreased than those in wild-type and heterozygous mice, the substantial amounts of BH4 were remained even 17 days after delivery. Spr-null mice exhibited severe monoamine deficiencies and a tremor-like phenotype after weaning. The amount of TH protein in the brain of Spr-null mice was less than 10% of wild-type, while TH protein in the adrenal, phenylalanine hydroxylase protein in the liver, and nNOS in the brain were not altered. These data suggest an essential role of SPR in the biosynthesis of BH4, and that the SPR gene could be a candidate gene for PARK3.

Original languageEnglish
Pages (from-to)787-792
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number4
DOIs
Publication statusPublished - 21-03-2008

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sepiapterin reductase
Tyrosine 3-Monooxygenase
Parkinson Disease
Brain
Genes
Biosynthesis
Proteins
Phenylalanine Hydroxylase
Metabolism
Liver
Tremor
Weaning
Enzymes
Phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Takazawa, Chisato ; Fujimoto, Kengo ; Homma, Daigo ; Ichinose, Chiho ; Nomura, Takahide ; Ichinose, Hiroshi ; Katoh, Setsuko. / A brain-specific decrease of the tyrosine hydroxylase protein in sepiapterin reductase-null mice-as a mouse model for Parkinson's disease. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 367, No. 4. pp. 787-792.
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A brain-specific decrease of the tyrosine hydroxylase protein in sepiapterin reductase-null mice-as a mouse model for Parkinson's disease. / Takazawa, Chisato; Fujimoto, Kengo; Homma, Daigo; Ichinose, Chiho; Nomura, Takahide; Ichinose, Hiroshi; Katoh, Setsuko.

In: Biochemical and Biophysical Research Communications, Vol. 367, No. 4, 21.03.2008, p. 787-792.

Research output: Contribution to journalArticle

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AU - Ichinose, Chiho

AU - Nomura, Takahide

AU - Ichinose, Hiroshi

AU - Katoh, Setsuko

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N2 - Sepiapterin reductase (SPR) is an enzyme that acts in the third and final step of tetrahydrobiopterin (BH4) biosynthesis. The human Spr gene locates within the region of 2.5 MB mapped to PARK3, an autosomal dominant form of familial Parkinson's diseases. In order to explore the role of SPR in the metabolism of BH4, we produced and analyzed Spr-deficient mice. Most of Spr-null mice survived beyond two weeks. Whereas the BH4 contents in the homozygous mutant mice were greatly decreased than those in wild-type and heterozygous mice, the substantial amounts of BH4 were remained even 17 days after delivery. Spr-null mice exhibited severe monoamine deficiencies and a tremor-like phenotype after weaning. The amount of TH protein in the brain of Spr-null mice was less than 10% of wild-type, while TH protein in the adrenal, phenylalanine hydroxylase protein in the liver, and nNOS in the brain were not altered. These data suggest an essential role of SPR in the biosynthesis of BH4, and that the SPR gene could be a candidate gene for PARK3.

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