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Chunk #25 — Discussion

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Genome-wide association discoveries of alcohol dependence.
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We carefully examined brain tissue of rats and mice using RNA-Seq and Affymetrix 3' level arrays respectively for the presence of mRNA coding for all known ADHs. We saw evidence for expression of ADH5 (Table 3), which was consistent with the work of Galter et al. (57) which examined the distribution of Class I, Class III and Class IV ADH's in tissues of mouse, rat and human brain and also found that the Class III ADH (equivalent to ADH5) was the major one appearing in the brain of mice, rats and humans. ADH5 in brain is not ubiquitously distributed but is evident in the dopaminergic neurons of the substantia nigra, the red nucleus, the hippocampus, cortex and the granule and Purkinje cells of the cerebellum. The common name for ADH5 is glutathione dependent formaldehyde dehydrogenase (chi polypeptide), and a role ascribed to this enzyme in brain has been in vitamin A metabolism, particularly the transformation of retinol to retinal. The retinal is transformed to retinoic acid which plays a major role in regulation of gene transcription. ADH5 has not been