Development of a humanized C1q A chain knock-in mouse: assessment of antibody independent beta-amyloid induced complement activation.

Molecular Immunology
Ming LiAndrea J Tenner

Abstract

Evidence has been accumulating for a role of inflammation in the development of Alzheimer's disease (AD), a progressive neurodegenerative disorder causing a common form of dementia in the elderly. C1q, part of the initiation component of the classical complement pathway (CCP), is associated with beta-sheet, fibrillar amyloid plaques in AD brain. In vitro, beta-amyloid peptide in fibrillar beta-sheet conformation (fAbeta) can activate CCP via interaction of specific negatively charged amino acids of the beta-amyloid fibril with human C1q. Previous results using peptide inhibitors led to the hypothesis that a highly positively charged domain consisting of three arginine residues, such as that present in the N-terminal collagen-like region of the human C1q A chain, may be critical for the activation event. However, mouse C1q A chain lacks two of the three arginines in the corresponding C1q A chain collagen-like region. To test the hypothesis that this divergent activation domain results in a weaker C' activation and thus may contribute to the lower neuronal loss observed in transgenic mouse models of AD, a partially humanized C1q A chain knock-in mouse was generated. The mouse C1q A chain gene was modified by homologous recombinat...Continue Reading

References

Jan 1, 1982·Annals of the New York Academy of Sciences·J E Volanakis
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·M LaksoH Westphal
Jun 27, 2002·Nature Neuroscience·Philip C WongDonald L Price
Sep 10, 2003·The Journal of Biological Chemistry·Christine GaboriaudGérard J Arlaud
Sep 15, 2004·Trends in Immunology·Uday KishoreGerard J Arlaud
Jun 25, 2005·Current Drug Targets. CNS and Neurological Disorders·Annemieke J M RozemullerPiet Eikelenboom
Sep 28, 2005·Expert Opinion on Therapeutic Targets·Jeffrey M CraftLinda J Van Eldik
Jun 5, 2007·Immunobiology·Robert B SimDaniel A Mitchell
Dec 18, 2007·Cell·Beth StevensBen A Barres

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Citations

Nov 18, 2009·Journal of Neuroinflammation·Julia ReichwaldMatthias Staufenbiel
Aug 16, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander H StephanBen A Barres
Jan 6, 2016·Biochemistry·Miho ChikazawaKoji Uchida
Jan 7, 2014·Trends in Neurosciences·Amy M Smith, Mike Dragunow
Aug 19, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mallary C Greenlee-WackerSuzanne S Bohlson

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