E. Kandil et al., STRUCTURAL AND PHYLOGENETIC ANALYSIS OF THE MHC CLASS I-LIKE FC RECEPTOR GENE, The Journal of immunology, 154(11), 1995, pp. 5907-5918
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.