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Neurobiol Dis. 2015 Jan;73:388-98. doi: 10.1016/j.nbd.2014.10.012. Epub 2014 Oct 29.

Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

Author information

1
UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.
2
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.
3
Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
4
Novartis Institutes for BioMedical Research, Novartis Campus, Basel, Switzerland.
5
Wallenberg Neuroscience Centre, Dept. of Experimental Medical Science, Brain Disease Biomarker Unit, Lund University, Lund, Sweden.
6
King's College London, Dept. of Medical and Molecular Genetics, Guy's Hospital, London, UK.
7
UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK. Electronic address: s.tabrizi@ucl.ac.uk.

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.

KEYWORDS:

Animal models of disease; Cytokines; Huntington's disease; Innate immune system; Myeloid cells; Neurodegeneration; Neuroinflammation

PMID:
25447230
PMCID:
PMC4262574
DOI:
10.1016/j.nbd.2014.10.012
[Indexed for MEDLINE]
Free PMC Article

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