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Genetic Deficiency of Complement Component 3 does not Alter Disease Progression in a Mouse Model of Huntington's Disease

Article type: Research Article

Authors: Larkin, Paul B.; | Muchowski, Paul J.; ; ;

Affiliations: Gladstone Institute of Neurological Disease, San Francisco, CA, USA | Neuroscience Graduate Program, University of California, San Francisco, CA, USA | Departments of Biochemistry and Biophysics and Neurology, University of California, San Francisco, CA, USA | The Taube-Koret Center for Huntington's Disease Research, San Francisco, CA, USA

Note: [] Correspondence to: Paul J. Muchowski, Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA. Tel.: +1 415 734 2000; E-mail: [email protected]

Keywords: Complement C3, Huntington disease, neurodegenerative diseases, immunity, innate

DOI: 10.3233/JHD-2012-120021

Journal: Journal of Huntington's Disease, vol. 1, no. 1, pp. 107-118, 2012

Published: 2012
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Abstract

Several genes and proteins of the complement cascade are present at elevated levels in brains of patients with Huntington's disease (HD). The complement cascade is well characterized as an effector arm of the immune system, and in the brain it is important for developmental synapse elimination. We hypothesized that increased levels of complement in HD brains contributes to disease progression, perhaps by contributing to synapse elimination or inflammatory signaling. We tested this hypothesis in the R6/2 mouse model of HD by crossing mice deficient in complement component 3 (C3), a crucial complement protein found at increased levels in HD brains, to R6/2 mice and monitoring behavioral and neuropathological disease progression. We found no alterations in multiple behavioral assays, weight or survival in R6/2 mice lacking C3. We also quantified the expression of several complement cascade genes in R6/2 brains and found that the large scale upregulation of complement genes observed in HD brains is not mirrored in R6/2 brains. These data show that C3 deficiency does not alter disease progression in the R6/2 mouse model of HD.

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