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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalJournal of Experimental and Clinical Medicine(Taiwan)
Volume2
Issue number5
DOIs
Publication statusPublished - Oct 2010

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Ethylnitrosourea
Proteome
Fatty Acids
Genes
Proteomics
Phenotype
Glycogen Synthase
Volatile Fatty Acids
Alkylating Agents
Mitochondrial Proteins
Point Mutation
Mutagenesis
Protein Kinases
Isoenzymes
Sequence Analysis
Electrophoresis
Mass Spectrometry
Lasers
Down-Regulation
Adenosine Triphosphate

Keywords

  • ENU mice
  • Proteomic
  • Short chain fatty acid

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Screening of ethylnitrosourea mice with fatty acid oxidation disorders by a candidate gene approach after proteome analysis. / Shih, Chun Kuang; Chen, Chiao-Ming; Chen, Yi Chun; Huang, Hsiao Chen; Chen, Yuang Tsong; Li, Sing Chung.

In: Journal of Experimental and Clinical Medicine(Taiwan), Vol. 2, No. 5, 10.2010, p. 231-238.

Research output: Contribution to journalArticle

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