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Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity1998; 9: 143\u201350","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"key\n\t\t\t\t20180712074205_B90","doi-asserted-by":"crossref","unstructured":"Mabbott NA, Bruce ME, Botto M, Walport MJ, Pepys MB. Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med2001; 7: 485\u20137","DOI":"10.1038\/86562"},{"key":"key\n\t\t\t\t20180712074205_B91","doi-asserted-by":"crossref","unstructured":"Park SY, Ueda S, Ohno H et al. Resistance of Fc receptor-deficient mice to fatal glomerulonephritis. J Clin Invest1998; 102: 1229\u201338","DOI":"10.1172\/JCI3256"},{"key":"key\n\t\t\t\t20180712074205_B92","doi-asserted-by":"crossref","unstructured":"Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV. Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. 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