BMC neuroscience, 2010-11, Vol.11 (1), p.143-143, Article 143
2010
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- Autor(en) / Beteiligte
- Titel
- Viable mouse gene ablations that robustly alter brain Aβ levels are rare
- Ist Teil von
- BMC neuroscience, 2010-11, Vol.11 (1), p.143-143, Article 143
- Ort / Verlag
- England: BioMed Central
- Erscheinungsjahr
- 2010
- Quelle
- SpringerLink
- Beschreibungen/Notizen
- Accumulation of amyloid-β (Aβ) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of Aβ, but not all are equally tractable for drug discovery. To search for novel targets that affect brain Aβ without causing toxicity, we screened mouse brain samples from 1930 novel gene knock-out (KO) strains, representing 1926 genes, using Aβ ELISA assays. Although robust Aβ lowering was readily apparent in brains from a BACE1 KO strain, none of the novel strains exhibited robust decreases in brain Aβ, including a GPR3 KO strain, which had previously been proposed as an Aβ target. However, significantly increased Aβ was observed in brain samples from two KO strains, corresponding to genes encoding the glycosylphosphatidylinositol mannosyl transferase PIGZ and quinolinate phosphoribosyltransferase (QPRT). Thus, gene ablations that are permissive for mouse survival and that also have a robust effect on Aβ levels in the brain are rare.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1471-2202eISSN: 1471-2202DOI: 10.1186/1471-2202-11-143Titel-ID: cdi_doaj_primary_oai_doaj_org_article_eb1b8cb6800c41798465e3ffd70625c3
- Format
- –
- Schlagworte
- Ablation, Alzheimer's disease, Amyloid beta-Peptides - biosynthesis, Amyloid beta-Peptides - metabolism, Amyloid beta-Protein Precursor - biosynthesis, Amyloid beta-Protein Precursor - metabolism, Amyloid Precursor Protein Secretases - genetics, Animals, Aspartic Acid Endopeptidases - genetics, Biosynthesis, Disease Models, Animal, Enzyme-linked immunosorbent assay, Enzymes, Gene Knockout Techniques - methods, Genes, Genetic Testing - methods, Glycosylphosphatidylinositol, Kinases, Mannosyltransferases - genetics, Metabolism, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Neurodegenerative diseases, Pentosyltransferases - genetics, Peptide Fragments - biosynthesis, Peptide Fragments - metabolism, Peptides, Phosphoribosyltransferase, Proteins, Quinolinate phosphoribosyltransferase, Toxicity, β-Amyloid, β-Site APP-cleaving enzyme 1