Screening of ethylnitrosourea mice with fatty acid oxidation disorders by a candidate gene approach after proteome analysis

Chun Kuang Shih, Chiao-Ming Chen, Yi Chun Chen, Hsiao Chen Huang, Yuang Tsong Chen, Sing Chung Li

研究成果: 雜誌貢獻文章同行評審

摘要

Background/Purpose: Ethylnitrosourea (ENU) is an alkylating agent and primarily induces point mutations such as AT to TA transversions and AT to GC transitions. Due to its high mutagenicity, ENU mouse mutagenesis enables the generation and identification of mouse mutants with aberrance in various phenotypes and to identify novel genes relevant for the expression of the phenotype. The purpose of this study was to investigate the candidate genes involved in fatty acid oxidation disorders by the proteomic approach. Methods: We screened ENU mice from 39 families from previously published data and identified two mutant mice that had a striking elevation in blood C4-OH short chain fatty acids compared with ENU controls. Total mitochondrial proteins were extracted from the gastrocnemius for two-dimensional electrophoresis, and two downregulated proteins, adenylate kinase isoenzyme 1 (AK1) and adenosine-5'-triphosphate (ATP) synthase D chain (ATP5H), were identified in the mutant mice through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: After genomic polymerase chain reaction and direct sequencing of Ak1 and Atp5h, no variation was found in both gene sequence analyses. Conclusion: Proteomic profiling can be a useful approach for detecting dynamic protein expression in ENU-induced mice. It is important to further clarify mechanisms of the mutant C4-OH disorder responsible for this expression.
原文英語
頁(從 - 到)231-238
頁數8
期刊Journal of Experimental and Clinical Medicine(Taiwan)
2
發行號5
DOIs
出版狀態已發佈 - 十月 2010

ASJC Scopus subject areas

  • 醫藥 (全部)

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