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Series GSE55148 Query DataSets for GSE55148
Status Public on Jun 01, 2015
Title Mildly compromised tetrahydrobiopterin biosynthesis mouse mutants exhibit abnormal body fat distribution and abdominal obesity
Organism Mus musculus
Experiment type Expression profiling by array
Summary Tetrahydrobiopterin (BH4) is an essential cofactor for several metabolic enzymes, including the aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and NO synthases. BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters. In contrast, augmentation of BH4 by pharmacological supplementation or stimulation of its biosynthesis is thought to correct eNOS dysfunction, to protect from (cardio) vascular disease and/or to prevent from abdominal obesity and development of the metabolic syndrome. We have previously reported that complete Pts knock-out (ko) mice die after birth (Elzaouk et al JBC 2003). Here we generated a murine Pts-knock-in (ki) allele expressing a PTPS-p.Arg15Cys mutant enzyme with low residual activity (12% of wild-type in vitro) and investigated heterozygous Pts-ko/wt, homozygous Pts-ki/ki and compound heterozygous Pts-ki/ko mutant mice. All mice were viable and, depending on the severity of the Pts alleles, exhibited up to 90% reduction of PTPS activity in liver and brain tissues concomitant with high neopterin, but neither an elevation of blood L-Phe, nor a decrease in brain monoamine neurotransmitters dopamine or serotonin. Upon a standard systemic and comprehensive phenotyping of Pts-ki/ki mice, we found alterations in energy metabolites with reduced body mass, higher fat content, lower lean mass, and increased blood glucose and cholesterol in mutant animals. Furthermore, heterozygous Pts-ko/wt and/or homozygous Pts-ki/ki mice exhibited increased body weight and elevated intra-abdominal fat tissue when fed with normal chow or high fat diet. We conclude that a reduced BH4-biosynthetic activity in mice leads to abnormal body fat distribution and abdominal obesity potentially through a mildly compromised eNOS function.
Overall design Total RNA obtained from 4 male homozgous ki and 4 male wildtype mice
Contributor(s) Beckers J, Horsch M
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Submission date Feb 19, 2014
Last update date Jun 14, 2018
Contact name Martin Irmler
Organization name Helmholtz Zentrum M√ľnchen GmbH
Department Institute of Experimental Genetics
Lab Gene Regulation & Epigenetics
Street address Ingolstaedter Landstrasse 1
City Neuherberg
State/province Bayern
ZIP/Postal code 85764
Country Germany
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM1330534 brain_wt_rep1 [BH4 study]
GSM1330535 brain_wt_rep2 [BH4 study]
GSM1330536 brain_wt_rep3 [BH4 study]
BioProject PRJNA238629

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55148_RAW.tar 3.1 Mb (http)(custom) TAR
GSE55148_non-normalized_data.txt.gz 2.5 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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