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. 1996 Mar 5;93(5):2131–2136. doi: 10.1073/pnas.93.5.2131

Enhanced and accelerated lymphoproliferation in Fas-null mice.

M Adachi 1, S Suematsu 1, T Suda 1, D Watanabe 1, H Fukuyama 1, J Ogasawara 1, T Tanaka 1, N Yoshida 1, S Nagata 1
PMCID: PMC39922  PMID: 8700897

Abstract

Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.

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