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Animal models of inherited complement deficiency
1Department of Rheumatology, Nevill Hall Hospital, Brecon Road, Abergavenny, NP7 7EG, UK. lintons@doctors.org.uk
Abstract:
The initial description of murine strains deficient in complement component C5 has been followed by the recognition in a range of animal species of a variety of natural complement component deficiencies, many of which have been characterized at the molecular level. The use of such species in inflammatory and infectious experimental models has led to significant progress in understanding the role of specific complement factors (and pathways) in disease pathogenesis. Deficiencies of early complement factors are characterized by impairment of immune response, possibly due to defective processing of immune complexes. Complete (but not partial) deficiency of the central component C3 predisposes affected animals to significant risk of infection and renal disease. Studies in species deficient in the terminal pathway component C6 are particularly relevant for investigating the pathogenetic role of the terminal membrane attack complex (MAC), implicating it as a causative agent in diverse inflammatory insults such as reperfusion injury, glomerular damage, and xenograft hyperacute rejection. Further investigations in such naturally deficient strains, added to results derived from studies in knockout animals, are likely to expand our understanding of the role of the activated complement system in experimental inflammatory disease, with significant potential implications for the treatment of human disease.
Insights
Animal models with complement deficiencies, like C3 and C6, are crucial for understanding inflammation and infection. These studies reveal the complement system
Area of Science:
- Immunology
- Molecular Biology
- Pathogenesis Research
Background:
- Natural deficiencies in complement components have been identified across various animal species.
- These deficiencies are often characterized at the molecular level, providing insights into complement system function.
- Previous research has utilized murine strains deficient in complement component C5.
Purpose of the Study:
- To explore the role of specific complement factors and pathways in disease pathogenesis using naturally deficient animal models.
- To investigate the pathogenetic role of the terminal membrane attack complex (MAC) in inflammatory conditions.
- To advance understanding of the activated complement system in experimental inflammatory diseases.
Main Methods:
- Characterization of natural complement component deficiencies in various animal species.
- Utilizing animal models with deficiencies in early complement factors, C3, and C6.
- Integrating findings from naturally deficient strains with studies on knockout animals.
Main Results:
- Deficiencies in early complement factors impair immune response, potentially due to defective immune complex processing.
- Complete C3 deficiency significantly increases susceptibility to infection and renal disease in affected animals.
- C6 deficiency studies implicate the MAC in inflammatory insults like reperfusion injury, glomerular damage, and xenograft rejection.
Conclusions:
- Naturally deficient animal models are invaluable tools for dissecting complement-mediated inflammation and infection.
- The terminal MAC plays a significant role in various inflammatory disease processes.
- Continued research in these models holds potential for developing novel therapeutic strategies for human diseases.
