GFP-tagged mutant prion protein forms intra-axonal aggregates in transgenic mice. 2008

Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

A nine-octapeptide insertional mutation in the prion protein (PrP) causes a fatal neurodegenerative disorder in both humans and transgenic mice. To determine the precise cellular localization of this mutant PrP (designated PG14), we have generated transgenic mice expressing PG14-EGFP, a fluorescent fusion protein that can be directly visualized in vivo. Tg(PG14-EGFP) mice develop an ataxic neurological illness characterized by astrogliosis, PrP aggregation, and accumulation of a partially protease-resistant form of the mutant PrP. Strikingly, PG14-EGFP forms numerous fluorescent aggregates in the neuropil and white matter of multiple brain regions. These aggregates are particularly prominent along axonal tracts in both brain and peripheral nerve, and similar intracellular deposits are visible along the processes of cultured neurons. Our results reveal intra-axonal aggregates of a mutant PrP, which could contribute to the pathogenesis of familial prion disease by disrupting axonal transport.

UI MeSH Term Description Entries
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D011328 Prions Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL. Mink Encephalopathy Virus,Prion,Encephalopathy Virus, Mink
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002479 Inclusion Bodies A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed) Cellular Inclusions,Cytoplasmic Inclusions,Bodies, Inclusion,Body, Inclusion,Cellular Inclusion,Cytoplasmic Inclusion,Inclusion Body,Inclusion, Cellular,Inclusion, Cytoplasmic,Inclusions, Cellular,Inclusions, Cytoplasmic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings

Related Publications

Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
February 2006, Biochemical and biophysical research communications,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
August 2004, Neurobiology of disease,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
April 1997, Protein science : a publication of the Protein Society,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
June 2005, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
December 1990, Science (New York, N.Y.),
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
January 2007, Journal of molecular neuroscience : MN,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
September 1994, Proceedings of the National Academy of Sciences of the United States of America,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
June 2000, Neuropathology and applied neurobiology,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
January 2013, Neuroscience,
Andrea Z Medrano, and Sami J Barmada, and Emiliano Biasini, and David A Harris
January 2010, Current pharmaceutical biotechnology,
Copied contents to your clipboard!