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Behavior and immune status of MRL mice in the postweaning period
B Sakić1, H Szechtman, H Talangbayan
1Department of Biomedical Sciences, McMaster University, Hamilton, Canada.
Abstract:
The notion that the MRL-lpr substrain is a useful model of behavioral and cognitive deficits found in systemic autoimmune diseases is supported 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 MRL-lpr mice is the result of the autoimmune process itself or reflects a subtle difference in genetic background or both. To address the question whether MRL-lpr mice are born with behavioral dysfunction the present study compares the behavior of the two MRL substrains in the early postweaning period, when their immune status does not show detectable difference. Results show that the prediseased (4- to 6-week-old) MRL-lpr mice are not distinguishable from the congenic MRL +/+ controls on most behavioral measures except for speed of locomotion and novelty-induced hyperactivity in activity monitors. The immune status of the two substrains is also similar except for a lower hematocrit in the MRL-lpr group. Surprisingly, low amounts of antinuclear and brain-reactive antibodies (possibly transferred from diseased mothers) were detected in the serum of about 50% of the mice in both groups. The lack of major differences in behavior in the premorbid period suggests that appearance of previously reported behavioral dysfunction in the disease state reflects the presence of autoimmunity, time-determined genetic activation, or both.
Insights
MRL-lpr mice show no significant behavioral differences before disease onset, suggesting autoimmunity causes later deficits. This research clarifies the MRL-lpr mouse model for autoimmune disease studies.
Area of Science:
- Immunology
- Neuroscience
- Behavioral Science
Background:
- The MRL-lpr mouse strain is a model for systemic autoimmune diseases.
- Previous studies indicated behavioral and cognitive deficits in MRL-lpr mice.
Purpose of the Study:
- To determine if MRL-lpr mice exhibit behavioral dysfunction at birth.
- To differentiate between autoimmune effects and genetic background differences on behavior.
Main Methods:
- Comparison of MRL-lpr and MRL +/+ mice behavior in the early postweaning period (4-6 weeks).
- Assessment of immune status, including hematocrit and antibody presence.
- Behavioral testing using activity monitors to measure locomotion and hyperactivity.
Main Results:
- MRL-lpr mice showed no major behavioral differences compared to controls before disease onset.
- Slight differences observed in locomotion speed and novelty-induced hyperactivity.
- Similar immune status except for lower hematocrit in MRL-lpr mice; some cross-maternal antibody transfer noted.
Conclusions:
- The behavioral dysfunction observed in MRL-lpr mice likely emerges with the development of autoimmunity or genetic activation.
- The MRL-lpr mouse model's behavioral changes are primarily linked to the autoimmune process rather than inherent genetic differences.
- Further research is needed to fully elucidate the interplay between autoimmunity and behavior in this model.