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

Marieta M. Ruseva, Timothy R. Hughes, Rossen M. Donev, Baalasubramanian Sivasankar, Matthew C. Pickering, Xiaobo Wu, Claire L. Harris, B. Paul Morgan

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)803-811
Number of pages9
JournalMolecular Immunology
Volume46
Issue number5
DOIs
StatePublished - Feb 1 2009

Keywords

  • Complement
  • Crry
  • Knockout
  • Mouse

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    Ruseva, M. M., Hughes, T. R., Donev, R. M., Sivasankar, B., Pickering, M. C., Wu, X., Harris, C. L., & Morgan, B. P. (2009). Crry deficiency in complement sufficient mice: C3 consumption occurs without associated renal injury. Molecular Immunology, 46(5), 803-811. https://doi.org/10.1016/j.molimm.2008.09.003