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

Biochemical and Biophysical Research Communications
Chisato TakazawaSetsuko Katoh

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 2.5MB 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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Citations

May 12, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Paul M A AntonyRudi Balling
Nov 11, 2010·The Journal of Biological Chemistry·Daigo HommaHiroshi Ichinose
Jul 29, 2011·Autophagy·Sang Su KwakCheol O Joe
Feb 27, 2013·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Keun-Sung LeeHak Rim Kim
Dec 25, 2008·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Hiroshi IchinoseChiho Sumi-Ichinose
Aug 1, 2020·Journal of Cellular and Molecular Medicine·Yao WuMeixiao Zhan
Apr 30, 2015·Proteomics. Clinical Applications·Daniel Martins-de-SouzaChristoph W Turck
Mar 23, 2017·Physiological Reports·Chiho Sumi-IchinoseKazunao Kondo

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