C3aR Knock-Out Mice
Inventors: Craig Gerard
Invention Types: Research Tool
Research Areas: Allergy/Respiratory/Pulmonary Disease, Cardiovascular/Cardiology, Degenerative Disease
Keywords: Animal Model (mouse), Drug Discovery, Drug ScreeningFor More Information Contact: Khunkhun, Rajinder
The complement system is a biochemical cascade that helps clear pathogens from an organism and it bridges the innate and adaptive immune system. The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens. During complement activation, anaphylatoxins, such as C3a, are released, eventually leading to the destruction of the pathogen by the cell-killing membrane attack complex. Dr. Gerard generated mice deficient in the G protein-coupled receptor for C3a (C3aR) by homologous recombination. These mice were born at the expected mendelian ratios, showed no overt developmental or morphologic abnormalities, and were fertile. Mice carrying the C3aR deletion were protected against the changes in lung physiology in a model of allergic airway disease. Human asthmatics have been shown to develop significant levels of ligand C3a following intrapulmonary deposition of allergen.
These results indicate that the C3aR -/- mice produced by Dr. Gerard may be useful to study the role of C3aR and C3a in the pathogenesis of human asthma. Asthma affects over 100 million people worldwide and its prevalence is expected to continue to rise. This mouse model could also be utilized to study other pathological conditions involving the complement system, such as autoimmune, inflammatory and ischemia/reperfusion injury-related diseases.
C3a on binding to C3aR mediates numerous proinflammatory activities. A better understanding of the role of C3aR should lead to the development of therapeutics strategies that would benefit millions of patients suffering from inflammatory and possibly degenerative diseases. A number of promising complement therapeutics are already in development, some of them targeting C3a or its receptor. The well characterized C3aR deficient mice generated by Dr. Gerard could be therefore be used for drug discovery, for drug screening and for studies of the pathogenesis of complement-related diseases.
Key Publications: Nature 406: 998-1001, 2000
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