| Role of the molybdoflavoenzyme aldehyde oxidase homolog 2 in the biosynthesis of retinoic acid: generation and characterization of a knockout mouse. | |
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MedLine Citation:
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PMID: 18981221 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mineko Terao; Mami Kurosaki; Maria Monica Barzago; Maddalena Fratelli; Renzo Bagnati; Antonio Bastone; Chiara Giudice; Eugenio Scanziani; Alessandra Mancuso; Cecilia Tiveron; Enrico Garattini |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-03 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 29 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-30 Completed Date: 2009-01-26 Revised Date: 2012-02-24 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 357-77 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Biology, Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging Aldehyde Oxidoreductases / genetics*, isolation & purification, metabolism* Animals Endocytosis / genetics Epidermis / anatomy & histology, chemistry, metabolism*, pathology Exocytosis / genetics Female Flavoproteins / genetics*, isolation & purification, metabolism* Gene Expression Profiling Gene Expression Regulation Harderian Gland / anatomy & histology, chemistry, metabolism* Hypertrophy / metabolism Lipids / genetics, physiology Male Mice Mice, Inbred Strains Mice, Knockout Oligonucleotide Array Sequence Analysis Retinaldehyde / metabolism Sebaceous Glands / metabolism Sex Characteristics Testosterone / metabolism Tretinoin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GTF03003//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Flavoproteins; 0/Lipids; 116-31-4/Retinaldehyde; 302-79-4/Tretinoin; 58-22-0/Testosterone; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.3.-/aldehyde oxidase homolog 2, mouse |
| Comments/Corrections | |
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