Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Gunn, Michael D.; Kyuwa, Shigeru; Tam, Carmen; Kakiuchi, Terutaka; Matsuzawa, Akio; Williams, Lewis T.; Nakano, Hideki

While we suggest that SLC is required for the normal homing of naive T cells and DCs to secondary lymphoid organs, we would emphasize that our findings do not constitute proof of this hypothesis. It is possible that the plt mutation directly affects the expression of a gene other than SLC or ELC which is responsible for some of the phenotypic abnormalities observed in plt mice. Although the plt mutation maps to the same genetic locus as SLC and plt mice express no detectable SLC, no DNA abnormality has been identified in these mice. Based on mapping data, the distance between the plt mutation and the SLC gene is between 1 and 1,000 kb. Given their normal SLC intron and exon sequences, we believe that the most likely cause of the lack of SLC expression in plt mice is a mutation involving a cis-acting regulatory region of the SLC gene. Such regions do not have to be in the immediate vicinity of the genes they regulate. For example, the deletion of a region 50 kb upstream of the human ␤-globin gene leads to a loss of its expression (53) . Because the plt mutation may involve a large deletion in the vicinity of the SLC gene, we cannot rule out the possibility that this defect involves more than one gene.