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Novel monoclonal antibodies against mouse C1q: characterisation and development of a quantitative ELISA for mouse C1q

Byrne, Robert A. J., Torvell, Megan, Daskoulidou, Nikoleta, Fathalla, Dina, Kokkali, Eirini, Carpanini, Sarah M. and Morgan, B. Paul 2021. Novel monoclonal antibodies against mouse C1q: characterisation and development of a quantitative ELISA for mouse C1q. Molecular Neurobiology 58 (9) , pp. 4323-4336. 10.1007/s12035-021-02419-5

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Abstract

Recent studies have identified roles for complement in synaptic pruning, both physiological during development and pathological in Alzheimer’s disease (AD). These reports suggest that C1q initiates complement activation on synapses and C3 fragments then tag them for removal by microglia. There is an urgent need to characterise these processes in rodent AD models; this requires the development of reagents and methods for detection and quantification of rodent C1q in fluids and pathological tissues. These will enable better evaluation of the role of C1q in disease and its value as disease biomarker. We describe the generation in C1q-deficient mice of novel monoclonal antibodies against mouse and rat C1q that enabled development of a sensitive, specific, and quantitative ELISA for mouse and rat C1q capable of measuring C1q in biological fluids and tissue extracts. Serum C1q levels were measured in wild-type (WT), C1q knockout (KO), C3 KO, C7 KO, Crry KO, and 3xTg and APPNL-G-F AD model mice through ageing. C1q levels significantly decreased in WT, APPNL-G-F, and C7 KO mice with ageing. C1q levels were reduced in APPNL-G-F compared to WT at all ages and in 3xTg at 12 months; C3 KO and C7 KO, but not Crry KO mice, also demonstrated significantly lower C1q levels compared to matched WT. In brain homogenates, C1q levels increased with age in both WT and APPNL-G-F mice. This robust and adaptable assay for quantification of mouse and rat C1q provides a vital tool for investigating the expression of C1q in rodent models of AD and other complement-driven pathologies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Springer
ISSN: 0893-7648
Date of First Compliant Deposit: 26 January 2022
Date of Acceptance: 30 April 2021
Last Modified: 29 Jan 2022 11:54
URI: https://orca.cardiff.ac.uk/id/eprint/146987

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