Enlarged spleens without enlarged lymph nodes in tlr3(-/-)pkr(-/-) mice

Initial phenotypic studies in a mouse containing mutations in both toll-like receptor 3 (TLR3) and RNA-dependent protein kinase R (PKR) revealed comparable spleen and bone marrow cell populations in tlr3(-/-), pkr(-/-), and tlr3(-/-)pkr(-/-) mice to wild-type controls. Splenomegaly developing between 8 and 10 weeks of age was observed in tlr3(-/-) and tlr3(-/-)pkr(-/-) mice but not in wild-type or pkr(-/-) mice. Palpably enlarged cervical, axillary, and inguinal lymph nodes accompanied by enlarged spleens were observed in 12-18-week-old tlr3(-/-) mice at a higher frequency compared with other genotypes. The enlarged spleens and lymph nodes observed in tlr3(-/-) mice were accompanied by destruction of organ architecture and lymphocyte infiltration. However, the enlargement of these organs was not the result of clonal proliferation of one lymphocyte subset. It is likely this phenotype is a result of TLR3 deficiency in combination with an additional, uncharacterized genetic defect or the presence of an infectious agent. These data also suggest that PKR may have a role in preventing progression from splenomegaly to lymphadenopathy in these mice.