Knock-in mice reveal nonsense-mediated mRNA decay in the brain
| Autor: | Brigitte L. Kieffer, Candice Contet, Andrée Dierich |
|---|---|
| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Institut Clinique de la Souris (ICS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
MESH: Mutation
RNA Stability Nonsense-mediated decay Mutant Receptors Opioid mu Down-Regulation MESH: Receptors Opioid mu Cycloheximide Biology MESH: Down-Regulation 03 medical and health sciences chemistry.chemical_compound Mice MESH: Brain 0302 clinical medicine Endocrinology Gene knockin Genetics Animals MESH: Animals RNA Messenger MESH: Codon Nonsense MESH: Cycloheximide Gene MESH: Mice 030304 developmental biology MESH: RNA Messenger Protein Synthesis Inhibitors 0303 health sciences Messenger RNA MESH: Protein Synthesis Inhibitors Brain MESH: RNA Stability [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology Molecular biology Stop codon mRNA surveillance chemistry Codon Nonsense Mutation 030217 neurology & neurosurgery |
| Zdroj: | Genesis Genesis, Wiley-Blackwell, 2007, 45 (1), pp.38-43. ⟨10.1002/dvg.20263⟩ |
| ISSN: | 1526-954X 1526-968X |
| DOI: | 10.1002/dvg.20263⟩ |
| Popis: | Nonsense-mediated mRNA decay (NMD) is a process of mRNA surveillance that degrades transcripts harboring a premature termination codon (PTC). Mammalian NMD was mostly studied in cultured cells so far and there was no direct evidence yet that NMD could operate in the brain. We introduced, by homologous recombination in mouse, a PTC in the mu opioid receptor gene (mor). mor transcript was severely downregulated in the brain of these knock-in mice. A systemic cycloheximide treatment significantly increased the level of the mutant mRNA, suggesting NMD involvement. To further corroborate this hypothesis, we generated a second knock-in mouse line where the PTC was placed at 10 instead of 96 nucleotides from the downstream splice junction. As predicted by the “termination codon position rule” established in vitro, mor transcript brain expression was rescued to wild-type level. These knock-in mouse lines will be valuable models to better understand and manipulate NMD in vivo. genesis 45:38–43, 2007. © 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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