Crry deficiency in complement sufficient mice: C3 consumption occurs without associated renal injury

Ruseva, Marieta Milkova, Hughes, Timothy Richard ORCID: https://orcid.org/0000-0003-2348-3490, Donev, Rossen Mintchev, Baalasubramanian, Sivasankar, Pickering, Matthew C., Wu, Xiaobo, Harris, Claire Louise and Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676 2009. Crry deficiency in complement sufficient mice: C3 consumption occurs without associated renal injury. Molecular Immunology 46 (5) , pp. 803-811. 10.1016/j.molimm.2008.09.003

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Abstract

The rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry) is critical for complement homeostasis. Gene deletion is 100% embryonically lethal; Crry-deficient (Crry(-/-)) mice were rescued by back-crossing onto C3 deficiency, confirming that embryo loss was complement mediated. In order to rescue viable Crry(-/-) mice without deleting C3, we have tested inhibition of C5 during gestation. Crry(+/-) females were given neutralizing anti-C5 mAb immediately prior to mating with Crry(+/-) males and C5 inhibition maintained through pregnancy. A single, healthy Crry(-/-) female was obtained and mating with Crry(+/-) males yielded healthy litters containing equal numbers of Crry(+/-) and Crry(-/-) pups. Inter-crossing Crry(-/-) mice yielded healthy litters of expected size. Although the mice were not anemic, exposure of Crry(-/-) erythrocytes to normal mouse serum caused C3 deposition and lysis, while transfusion into normal or C6(-/-) mice resulted in rapid clearance. Complement activity and C3 levels in Crry(-/-) mice were markedly reduced. Comparison with factor H deficient (CfH(-/-)) mice revealed similar levels of residual C3; however, unlike the CfH(-/-) mice, Crry(-/-) mice showed no evidence of renal injury, demonstrating distinct roles for these regulators in protecting the kidney.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Complement; Crry; Knockout; Mouse
Publisher:	Elsevier
ISSN:	0161-5890
Last Modified:	06 Dec 2022 09:40
URI:	https://orca.cardiff.ac.uk/id/eprint/25501

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