Aldehyde oxidase homologue 2 (Aoh2) knockout mouse and retinoic acid synthesis

The mouse aldehyde oxidase, Aoh2 (aldehyde oxidase homolog 2), is a molybdo-flavoenzyme. Harderian glands are the richest source of Aoh2, although the protein is detectable also in sebaceous glands, epidermis and other keratinized epithelia. The levels of Aoh2 in the Harderian gland and skin are controlled by genetic background, being maximal in CD1 or C57BL/6 and minimal in DBA/2, CBA or 129/Sv strains. Testosterone is a negative regulator of Aoh2 in Harderian glands. Homogenously purified Aoh2 oxidizes retinaldehyde into retinoic acid efficiently, while it is devoid of pyridoxal oxidizing activity, unlike other aldehyde oxidases. Aoh2 knockout mice are viable and fertile, although they have an absolute deficit of retinaldehyde oxidase activity in the Harderian gland, decreased retinoic acid levels, and down-regulation of retinoid-dependent genes. The Harderian gland’s transcriptome of knockout mice is characterized by perturbations in pathways controlling lipid homeostasis and cellular secretion. This is particularly evident in sexually immature animals. Lower amounts of retinoic acid are also observed in the skin of Aoh2-/- animals. Knockout mice have thickening of the epidermis in basal conditions and after UV light exposure. This has correlates in the skin transcriptome, which shows enrichment and overall up-regulation of genes involved in hypertrophic responses. Keywords: Gene knockout study Harderian Gland - Animals were divided into four groups: male and female, before and after sexual maturation (5-6 and 7-9 weeks, respectively). 3-5 animals per group were used. Each couple of samples from WT and KO mice, age and sex matched, and where possible, from brothers, were hybridized on the same slide, in dye-swapped duplicates, for a total of 30 microarrays. Skin – Skin samples from 4 WT and 4 KO adult female animals were taken, age matched (sisters, whenever possible), and hybridized on the same slide with a balanced dye design, for a total of 4 microarrays.