Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice

Oct 3, 2006Alcoholism, clinical and experimental research

Brain gene patterns for alcohol and aldehyde metabolism in two mouse strains

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Abstract

Significantly higher expression of mRNA for aldehyde dehydrogenase 2 (ALDH2) was observed in the whole brains of DBA/2 mice compared to C57BL/6 mice.

No significant differences were found in gene expression of alcohol dehydrogenases or related enzymes between C57BL/6 and DBA/2 mice.
DBA/2 mice exhibited higher levels of aldehyde dehydrogenase 2 (ALDH2) protein, which is important for breaking down acetaldehyde.
Higher expression of aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA was observed in DBA/2 mice with one platform, but not consistently across all methods.
C57BL/6 mice showed significantly higher levels of aldehyde dehydrogenase 7A1 (ALDH7A1) mRNA and protein compared to DBA/2 mice.
The expression differences may be associated with variations in acetaldehyde metabolism and alcohol preference between the two mouse strains.

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BACKGROUND: Differences in ethanol metabolizing enzymes expressed in brain have been suggested to contribute to the significant differences in ethanol (alcohol) preference between inbred C57BL/6 and DBA/2 mouse strains.

METHODS: We have utilized 2 different platforms of oligonucleotide microarray technology (CodeLink UniSet I BioArray from G.E. Healthcare and MG U74A v2.0 from Affymetrix) to simultaneously assess expression of alcohol and acetaldehyde metabolizing enzymes in the whole brain of naïve (no exposure to alcohol) C57BL/6 and DBA/2 mice.

RESULTS: There were no significant differences between the 2 strains of mice in gene expression intensity for alcohol dehydrogenases (ADH), catalase, and a number of the cytochrome P450 family of genes, which can be involved in ethanol catabolism. However, significantly higher expression of mRNA for aldehyde dehydrogenase 2 (ALDH2), an isoform mainly responsible for the catabolism of acetaldehyde, was observed in whole brains of DBA/2 mice with both platforms. Aldehyde dehydrogenase 2 protein was also higher in DBA/2 brain. Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA was found to be higher in brains of DBA/2 mice, when measured with the CodeLink platform, but not when measured with Affymetrix arrays or quantitative reverse transcriptase-real-time polymerase chain reaction (qRT-PCR). The ALDH1A1 protein, however, reflected the results obtained with the CodeLink arrays and was higher in DBA/2 brain, compared with brains of C57BL/6 mice. In contrast, the expression intensity for the aldehyde dehydrogenase 7A1 (ALDH7A1) mRNA and protein was significantly higher in C57BL/6 mice than DBA/2 mice. These expression differences are consistent with more rapid metabolism of acetaldehyde in brains of DBA/2 mice.

CONCLUSIONS: The use of 2 different microarray platforms provides important cross-validation of many results, and some discrepancies can be resolved with qRT-PCR and immunoblotting. The expression differences that were validated may affect alcohol/aldehyde metabolism in brain and/or alcohol preference in the 2 strains of mice.

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Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice

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