BEHAVIOR AND IMMUNE STATUS OF MRL MICE IN THE POSTWEANING PERIOD

The notion that the MRl-lpr substrain is a useful model of behavioral and cognitive deficits found in systemic autoimmune diseases is suppor ted by the recent findings of behavioral dysfunction in autoimmune MRL -lpr mice compared to their congenic control MRL +/+ mice. However, it has not been established whether the altered behavioral profile in MR L-lpr mice is the result of the autoimmune process itself or reflects a subtle difference in genetic background or both. To address the ques tion whether MRL-lpr mice are born with behavioral dysfunction the pre sent study compares the behavior of the two MRL substrains in the earl y postweaning period, when their immune status does not show detectabl e difference. Results show that the prediseased (4- to 6-week-old) MRL -lpr mice are not distinguishable from the congenic MRL +/+ controls o n most behavioral measures except for speed of locomotion and novelty- induced hyperactivity in activity monitors. The immune status of the t wo substrains is also similar except for a lower hematocrit in the MRL -lpr group. Surprisingly, low amounts of antinuclear and brain-reactiv e antibodies (possibly transferred from diseased mothers) were detecte d in the serum of about 50% oof the mice in both groups. The lack of m ajor differences in behavior in the premorbid period suggests that app earance of previously reported behavioral dysfunction in the disease s tate reflects the presence of autoimmunity, time-determined genetic ac tivation, or both. (C) 1994 Academic Press, Inc.