Rd8 mutation in the Crb1 gene of CD11c-eYFP transgenic reporter mice results in abnormal numbers of CD11c-positive cells in the retina

There has been considerable debate about whether dendritic cells (DCs), which are potent antigen-presenting cells pivotal to adaptive immune responses, are present in CNS parenchyma. In studies aimed at answering this issue, we discovered that while the neural retina of young naive transgenic C57BL/6 CD11c-eYFP reporter mice contained more than 800 CD11c-positive cells/retina, these cells were virtually absent in C57BL/6 CD11c-DTR/GFP mice. Clinical fundus examination, confocal imaging of retinal whole mounts, and sections revealed colocalization of CD11c-positive cells with classic mild to severe retinal dystrophic lesions. Immunophenotypic analysis revealed that CD11c-positive cells in the neural retina of these mice had the characteristic profile of activated microglia and not DCs. Genotypic analysis confirmed that the cause of the retinal dystrophic lesions in CD11c-eYFP transgenic mice was the occurrence of the Crb1(rd8) mutation, which affects all mice of the C57BL/6N strain but not the C57BL/6J strain. Comparison of 2 different types of CD11c reporter transgenic mice revealed that a mutation in the Crb1 gene leads to retinal degeneration resulting in the activation of large numbers of local microglia that could be readily mistaken for CD11c-positive putative DCs.