title: Inclusions of R6/2 Mice Are Not Amyloid and Differ Structurally from Those of Huntington Disease Brain.
abstract: R6/2 mice contain an N-terminal fragment of human huntingtin with an expanded polyQ and develop a neurological disease resembling Huntington disease. Although the brain of R6/2 mice contains numerous inclusions, there is very little neuronal death. In that respect, R6/2 mice differ from patients with Huntington disease whose striatum and cerebral cortex develop inclusions associated with extensive neuronal loss. We have previously demonstrated using synchrotron-based infrared microspectroscopy that the striatum and the cortex of patients with Huntington disease contained inclusions specifically enriched in amyloid β-sheets. We had concluded that the presence of an amyloid motif conferred toxicity to the inclusions. We demonstrate here by synchrotron based infrared microspectroscopy in transmission and attenuated total reflectance mode that the inclusions of R6/2 mice possess no detectable amyloid and are composed of proteins whose structure is not distinguishable from that of the surrounding soluble proteins. The difference in structure between the inclusions of patients affected by Huntington disease and those of R6/2 mice might explain why the former but not the latter cause neuronal death.
authors.affiliation: Centre National de la Recherche Scientifique/Université Paris Descartes , UMR 8118, Laboratoire de Physiologie Cérébrale, 75006 Paris, France.|Synchrotron SOLEIL , 91192 Gif-sur-Yvette, France.
authors.forename: William
authors.initials: W
authors.lastname: André
authors.affiliation: Synchrotron SOLEIL , 91192 Gif-sur-Yvette, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sandt
authors.affiliation: Centre National de la Recherche Scientifique/Université Paris Descartes , UMR 8118, Laboratoire de Physiologie Cérébrale, 75006 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Nondier
authors.affiliation: Centre National de la Recherche Scientifique/Université Paris Descartes , UMR 8118, Laboratoire de Physiologie Cérébrale, 75006 Paris, France.
authors.forename: Philippe
authors.identifier: 0000-0001-9586-0254
authors.initials: P
authors.lastname: Djian
authors.affiliation: Centre National de la Recherche Scientifique/Université Paris Descartes , UMR 8118, Laboratoire de Physiologie Cérébrale, 75006 Paris, France.
authors.forename: Guylaine
authors.initials: G
authors.lastname: Hoffner
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D000071058:Huntingtin Protein / Q000235:genetics* / Q000378:metabolism; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008853:Microscopy; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D025341:Principal Component Analysis; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; C086055:HTT protein, human; D000071058:Huntingtin Protein; D010455:Peptides; C097188:polyglutamine