title: Role of the molybdoflavoenzyme aldehyde oxidase homolog 2 in the biosynthesis of retinoic acid: generation and characterization of a knockout mouse.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy.
authors.forename: Mineko
authors.initials: M
authors.lastname: Terao
authors.forename: Mami
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Maria Monica
authors.initials: MM
authors.lastname: Barzago
authors.forename: Maddalena
authors.initials: M
authors.lastname: Fratelli
authors.forename: Renzo
authors.initials: R
authors.lastname: Bagnati
authors.forename: Antonio
authors.initials: A
authors.lastname: Bastone
authors.forename: Chiara
authors.initials: C
authors.lastname: Giudice
authors.forename: Eugenio
authors.initials: E
authors.lastname: Scanziani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mancuso
authors.forename: Cecilia
authors.initials: C
authors.lastname: Tiveron
authors.forename: Enrico
authors.initials: E
authors.lastname: Garattini
mesh_terms: D000375:Aging; D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D004705:Endocytosis / Q000235:genetics; D004817:Epidermis / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D005089:Exocytosis / Q000235:genetics; D005260:Female; D005420:Flavoproteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006243:Harderian Gland / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D006984:Hypertrophy / Q000378:metabolism; D008055:Lipids / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012172:Retinaldehyde / Q000378:metabolism; D012627:Sebaceous Glands / Q000378:metabolism; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D005420:Flavoproteins; D008055:Lipids; D013739:Testosterone; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C443117:aldehyde oxidase homolog 2, mouse; D012172:Retinaldehyde