Immunological characterization of C3H mice congenic for Fasˡᵖʳᶜᵍ, C3H/HeJ-Fasˡᵖʳᶜᵍ/Fasˡᵖʳᶜᵍ
2000
Yasuda, Takuwa | Zhang, Yan | Nagase, Hisashi | Kaneko, Tetsuya | Sayama, Kazutoshi | Hashimoto, Hajime | Matsuzawa, Akio
Fasˡᵖʳ(lpr) and Fasˡᵖʳᶜᵍ (lprᶜᵍ) are allelic mutations of the Fas gene that is involved in apoptosis or programmed cell death. Lpr greatly reduces the expression of functional Fas and lprᶜᵍ expresses the death domain-disabled, non-functional Fas on the cell surface. C3H/HeJ mice congenic for lprᶜᵍ (C3H-lprᶜᵍ) were established and compared with C3H/HeJ-lpr/lpr (C3H-lpr) mice for their immunological and pathological features. Lymphadenopathy, splenomegaly, development of CD4⁻CD8⁻B220⁺ or double-negative (DN) T cells, renal pathology, and lymphoid cell infiltration in the lung and liver were not significantly different between C3H-lprᶜᵍ and C3H-lpr mice. Noticeably, however, the production of serum immunoglobulin, autoantibodies against double-strand DNA and serum immune complexes were significantly lower in C3H-lprᶜᵍ than in C3H-lpr mice. The results indicate that the death signal through the death domain of Fas is responsible for lymphoproliferation due to the accumulation of DN T cells and suggest that the region of Fas outside the death domain may be involved in autoantibody production. The newly-developed congenic C3H-lprᶜᵍ mice will provide a powerful tool for research into the function of Fas apart from apoptosis.
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