STRUCTURAL AND PHYLOGENETIC ANALYSIS OF THE MHC CLASS I-LIKE FC RECEPTOR GENE

The intestinal epithelium of neonatal mice and rats expresses an Fc re ceptor that mediates selective uptake of IgG in mothers' milk. This re ceptor (FcRn), which helps newborn animals to acquire passive immunity , is an MHC class I-like heterodimer made up of a heavy chain and beta (2)-microglobulin. In the present study, we determined the genomic str ucture of a mouse gene (Fcm) encoding the heavy chain of FcRn. The ove rall exon-intron organization of the Fcrn gene was similar to that of the MHC class I gene, thus providing structural evidence that Fcrn is a bona fide class I gene. The 5'-flanking region of the Fcrn gene cont ained the binding motifs for two cytokine-inducible transcription fact ors, NF-IL6 and NF1. However, regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were abs ent. Phylogenetic tree analysis suggested that, like the MICA, AZGP1, and CD1 genes, the Fcrn gene diverged from MHC class I genes after the emergence of amphibians but before the split of placental and marsupi al mammals. Consistent with this result, Southern blot analysis with a mouse Fcrn cDNA probe detected cross-hybridizing bands in various mam malian species and chickens. Sequence analysis of the Fcrn gene isolat ed from eight mouse strains showed that the membrane-distal domain of FcRn has at least three amino acid variants. The fact that Fcrn is a s ingle copy gene indicates that it is expressed in both the neonatal in testine and the fetal yolk sac.