Role of the Molybdoflavoenzyme Aldehyde Oxidase Homolog 2 in the Biosynthesis of Retinoic Acid: Generation and Characterization of a Knockout Mouse
| Autor: | Antonio Bastone, Mineko Terao, Maddalena Fratelli, Eugenio Scanziani, Enrico Garattini, Cecilia Tiveron, Alessandra Mancuso, Mami Kurosaki, Renzo Bagnati, Chiara Giudice, Maria Monica Barzago |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Aging Retinoic acid Mice Inbred Strains Tretinoin Biology Exocytosis Transcriptome Mice Sebaceous Glands chemistry.chemical_compound Harderian gland Downregulation and upregulation medicine Animals Testosterone Molecular Biology Aldehyde oxidase Oligonucleotide Array Sequence Analysis Mice Knockout Sex Characteristics Flavoproteins Epidermis (botany) Harderian Gland Gene Expression Profiling Articles Hypertrophy Cell Biology Aldehyde Oxidoreductases Lipids Molecular biology Endocytosis Gene Expression Regulation chemistry Biochemistry Knockout mouse Retinaldehyde Female Epidermis medicine.drug |
| Zdroj: | Molecular and Cellular Biology. 29:357-377 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.01385-08 |
| Popis: | The mouse aldehyde oxidase AOH2 (aldehyde oxidase homolog 2) is a molybdoflavoenzyme. 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 and C57BL/6 and minimal in DBA/2, CBA, and 129/Sv strains. Testosterone is a negative regulator of AOH2 in Harderian glands. Purified AOH2 oxidizes retinaldehyde into retinoic acid, while it is devoid of pyridoxal-oxidizing activity. Aoh2(-/-) mice, the first aldehyde oxidase knockout animals ever generated, are viable and fertile. The data obtained for this knockout model indicate a significant role of AOH2 in the local synthesis and biodisposition of endogenous retinoids in the Harderian gland and skin. The Harderian gland's transcriptome of knockout mice demonstrates overall downregulation of direct retinoid-dependent genes as well as perturbations in pathways controlling lipid homeostasis and cellular secretion, particularly in sexually immature animals. The skin of knockout mice is characterized by thickening of the epidermis in basal conditions and after UV light exposure. This has correlates in the corresponding transcriptome, which shows enrichment and overall upregulation of genes involved in hypertrophic responses. |
| Databáze: | OpenAIRE |
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