1. Non-targeted metabolomics by high resolution mass spectrometry in HPRT knockout mice.
- Author
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Tschirner, Sarah K., Bähre, Heike, Kaever, Alexander, Schneider, Erich H., Seifert, Roland, and Kaever, Volkhard
- Subjects
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METABOLOMICS , *MASS spectrometry , *HYPERURICEMIA , *LESCH-Nyhan syndrome , *X chromosome , *PATHOLOGICAL physiology , *HIGH performance liquid chromatography , *PHENOTYPES - Abstract
Aims Lesch-Nyhan disease (LND) is characterized by hyperuricemia as well as neurological and neuropsychiatric symptoms including repetitive self-injurious behavior. Symptoms are caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as a result of a mutation on the X chromosome. To elucidate the pathophysiology of LND, we performed a metabolite screening for brain and serum extracts from HPRT knockout mice as an animal model for LND. Main methods Analyses were performed by high performance liquid chromatography (HPLC)-coupled quadrupole time-of-flight mass spectrometry (QTOF-MS). Key findings In brain extracts, we found six metabolites with significantly different contents in wild-type and HPRT-deficient mice. Two compounds we could identify as 5-aminoimidazole-4-carboxamide ribotide (AICAR) and 1-methylimidazole-4-acetic acid (1-MI4AA). Whereas AICAR was accumulated in brains of HPRT knockout mice, 1-MI4AA was decreased in these mice. Significance Both metabolites play a role in histidine metabolism and, as a consequence, histamine metabolism. AICAR, in addition, is part of the purine metabolism. Our findings may help to better understand the mechanisms leading to the behavioral phenotype of LND. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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