title: Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.
abstract: Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines. To further determine the degree to which these models recapitulate observations in HD patients, we evaluated various myeloid cell populations from different HD mouse models to determine whether they are similarly hyper-responsive, as well as measuring other aspects of myeloid cell function. Myeloid cells from each of the three mouse models studied, R6/2, HdhQ150 knock-in and YAC128, showed increased cytokine production when stimulated. However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells. Furthermore, macrophages isolated from R6/2 mice show increased levels of phagocytosis, similar to findings in HD patients. Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression.
authors.affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Träger
authors.affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Andre
authors.affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK; Wallenberg Neuroscience Centre, Dept. of Experimental Medical Science, Brain Disease Biomarker Unit, Lund University, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Magnusson-Lind
authors.affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.
authors.forename: James R C
authors.initials: JR
authors.lastname: Miller
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Colúm
authors.initials: C
authors.lastname: Connolly
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Campus, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weiss
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Campus, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grueninger
authors.affiliation: Wallenberg Neuroscience Centre, Dept. of Experimental Medical Science, Brain Disease Biomarker Unit, Lund University, Lund, Sweden.
authors.forename: Edina
authors.initials: E
authors.lastname: Silajdžić
authors.affiliation: King's College London, Dept. of Medical and Molecular Genetics, Guy's Hospital, London, UK.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.affiliation: King's College London, Dept. of Medical and Molecular Genetics, Guy's Hospital, London, UK.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
authors.affiliation: Wallenberg Neuroscience Centre, Dept. of Experimental Medical Science, Brain Disease Biomarker Unit, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
authors.affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK. Electronic address: s.tabrizi@ucl.ac.uk.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Animal models of disease; Cytokines; Huntington's disease; Innate immune system; Myeloid cells; Neurodegeneration; Neuroinflammation