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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-10886

Elzaouk, L; Leimbacher, W; Turri, M; Ledermann, B; Burki, K; Blau, N; Thony, B (2003). Dwarfism and low insulin-like growth factor-1 due to dopamine depletion in Pts-/- mice rescued by feeding neurotransmitter precursors and H4-biopterin. Journal of Biological Chemistry, 278(30):28303-28311.

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Abstract

The tetrahydrobiopterin (BH4) cofactor is essential for the biosynthesis of catecholamines and serotonin and for nitric-oxide synthase (NOS). Alterations in BH4 metabolism are observed in various neurological and psychiatric diseases, and mutations in one of the human metabolic genes causes hyperphenylalaninemia and/or monoamine neurotransmitter deficiency. We report on a knockout mouse for the Pts gene, which codes for a BH4-biosynthetic enzyme. Homozygous Pts-/- mice developed with normal morphology but died after birth. Upon daily oral administration of BH4 and neurotransmitter precursors the Pts-/- mice eventually survived. However, at sexual maturity (6 weeks) the mice had only one-third of the normal body weight and were sexually immature. Biochemical analysis revealed no hyperphenylalaninemia, normal brain NOS activity, and almost normal serotonin levels, but brain dopamine was 3% of normal. Low dopamine leads to impaired food consumption as reflected by the severe growth deficiency and a 7-fold reduced serum insulin-like growth factor-1 (IGF-1). This is the first link shown between 6-pyruvoyltetrahydropterin synthase- or BH4-biosynthetic activity and IGF-1.

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Laboratory Animal Science
04 Faculty of Medicine > Institute of Laboratory Animal Science
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:25 July 2003
Deposited On:25 Mar 2009 07:45
Last Modified:27 Nov 2013 23:38
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Elzaouk, L; Leimbacher, W; Turri, M; Ledermann, B; Burki, K; Blau, N; Thony, B (2003). Dwarfism and low insulin-like growth factor-1 due to dopamine depletion in Pts-/- mice rescued by feeding neurotransmitter precursors and H4-biopterin. Journal of Biological Chemistry, 278(30):28303-28311. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M303986200
PubMed ID:12734191
Citations:Web of Science®. Times Cited: 29
Google Scholar™
Scopus®. Citation Count: 27

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