TAILIEUCHUNG - Báo cáo khoa học: Disruption of the gene encoding 3b-hydroxysterol D14-reductase (Tm7sf2) in mice does not impair cholesterol biosynthesis

Tm7sf2gene encodes 3b-hydroxysterol D 14 -reductase (C14SR, DHCR14), an endoplasmic reticulum enzyme acting onD 14 -unsaturated sterol interme-diates during the conversion of lanosterol to cholesterol. The C-terminal domain of lamin B receptor, a protein of the inner nuclear membrane mainly involved in heterochromatin organization, also possesses sterol D 14 -reductase activity. | ễFEBS Journal Disruption of the gene encoding 3p-hydroxysterol D14-reductase Tm7sf2 in mice does not impair cholesterol biosynthesis Anna M. Bennati1 Gianluca Schiavoni1 Sebastian Franken2 Danilo Piobbico3 Maria A. Della Pa7ia3 Hnnatolla Pari ICA4 Pm ma Do Pahiani4 I ai I ra Ronorlotti5 a ri a Iiealla Ho A nnolio5 razia ưoiiaieua Vdiuso diiiiia L e rauiaiii Lauid Deneueiu Iviaiia XJ. vuseiia L e MHgeis Volkmar Gieselmann2 Giuseppe Servillo3 Tommaso Beccari1 and Rita Roberti1 1 Department of InternalMedicine University of Perugia Italy 2 Institut fur Physiologische Chemie Rheinische Friedrich-Wilhelms-Universitat Bonn Germany 3 Department of Clinicaland ExperimentalMedicine University of Perugia Italy 4 Department of PharmacologicalSciences University of Milan Italy 5 Department of ExperimentalMedicine University of Pavia Italy Keywords 3beta-hydroxysteroldelta14-reductase cholesterolbiosynthesis gene expression lamin B receptor Tm7sf2 Correspondence R. Roberti Department of InternalMedicine Laboratory of Biochemistry University of Perugia Via delGiochetto 06122 Perugia Italy Fax 39 075 585 7428 Tel 39 075 585 7426 E-mail roberti@ Received 24 May 2008 accepted 11 August 2008 doi Tm7sf2 gene encodes 3b-hydroxysterol A14-reductase C14SR DHCR14 an endoplasmic reticulum enzyme acting on A14-unsaturated sterol intermediates during the conversion of lanosterol to cholesterol. The C-terminal domain of lamin B receptor a protein of the inner nuclear membrane mainly involved in heterochromatin organization also possesses sterol A14-reductase activity. The subcellular localization suggests a primary role of C14SR in cholesterol biosynthesis. To investigate the role of C14SR and lamin B receptor as 3b-hydroxysterol A14-reductases Tm7sf2 knockout mice were generated and their biochemical characterization was performed. No Tm7sf2 mRNA was detected in the liver of knockout mice. Neither C14SR protein nor 3 b-hydroxysterol A14-reductase .

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