Brain abnormalities in immune defective mice

Mouse strains with or without immune disorders were examined in order to further assess the incidence of brain anomalies in immune-disordered strains. The brain was examined in Nissl-stained serial sections under a light microscope for the presence of abnormalities, with specific attention to ectopic collections of neurons in layer I of the neocortex, as reported in the autoimmune New Zealand Black (NZB) and BXSB strains. The present study was designed to survey additional strains with immune disorders (Snell dwarf, C57BL/6J-nu/nu, BALB/cByJ-nu/nu, and SJL) and 7 control strains without immune disorders. In addition, we attempted to replicate past findings in the highly affected BXSB strain and the MRL/1 strain, which develops autoimmune disease, but has a low incidence of brain abnormalities. The largest number of brain abnormalities (20-40%) were seen in the C57BL/6J-nu/nu, Snell dwarf and BXSB strains. The anomalies in the C57BL/6J-nu/nu and BXSB mice consisted of ectopic neurons in layer I of the neocortex, whereas the Snell dwarf mice had either neuron-free areas in the cortex, or rippling of cortical layers II-IV, and one case had agenesis of the corpus callosum. Between 4% and 8% of the mice from the SJL, MRL/1, and MRL +/+ strains had either neuron-free areas in the cortex or ectopic neurons in layer I. The BALB/cByJ-nu/nu and control strains did not have any cortical abnormalities. Future studies will be designed to determine whether immune-based alterations to the developing brain are responsible for the brain anomalies present in immune-disordered strains.