Specific Excision of the Selenocysteine tRNA (Trsp) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function*

نویسندگان

  • Bradley A. Carlson
  • Sergey V. Novoselov
  • Easwari Kumaraswamy
  • Byeong Jae Lee
  • Miriam R. Anver
  • Vadim N. Gladyshev
چکیده

From the ‡Section on the Molecular Biology of Selenium, Basic Research Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, 20892, §Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588, Laboratory of Molecular Genetics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea, and **Pathology/Histotechnology Laboratory, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702

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منابع مشابه

Specific excision of the selenocysteine tRNA[Ser]Sec (Trsp) gene in mouse liver demonstrates an essential role of selenoproteins in liver function.

Selenium is essential in mammalian embryonic development. However, in adults, selenoprotein levels in several organs including liver can be substantially reduced by selenium deficiency without any apparent change in phenotype. To address the role of selenoproteins in liver function, mice homozygous for a floxed allele encoding the selenocysteine (Sec) tRNA([Ser]Sec) gene were crossed with trans...

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Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism.

Selenium is incorporated into proteins as selenocysteine (Sec), which is dependent on its specific tRNA, designated tRNA([Ser]Sec). Targeted removal of the tRNA([Ser]Sec) gene (Trsp) in mouse hepatocytes previously demonstrated the importance of selenoproteins in liver function. Herein, analysis of plasma proteins in this Trsp knockout mouse revealed increases in apolipoprotein E (ApoE) that wa...

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A functional link between housekeeping selenoproteins and phase II enzymes.

Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated...

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The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice.

STAF [Sec (selenocysteine) tRNA gene transcription activating factor] is a transcription activating factor for a number of RNA Pol III- and RNA Pol II-dependent genes including the Trsp [Sec tRNA gene], which in turn controls the expression of all selenoproteins. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined. We generated transgenic mice expressing ...

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The distal sequence element of the selenocysteine tRNA gene is a tissue-dependent enhancer essential for mouse embryogenesis.

Appropriate expression of the selenocysteine tRNA (tRNA(Sec)) gene is necessary for the production of an entire family of selenoprotein enzymes. This study investigates the consequence of disrupting an upstream enhancer region of the mouse tRNA(Sec) gene (Trsp) known as the distal sequence element (DSE) by use of a conditional repair gene targeting strategy, in which a 3.2-kb insertion was intr...

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تاریخ انتشار 2004