Disease relevance of Fcgrt

• The neonatal Fc receptor is not required for mucosal infection by mouse mammary tumor virus [1].

High impact information on Fcgrt

• Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria [2].
• We show that IgG induces the same degree of suppression of the response to sheep erythrocytes in animals lacking the known IgG-binding receptors FcgammaRIIB, FcgammaRI + III, FcgammaRI + IIB + III, and FcRn (the neonatal Fc receptor) as in wild-type animals [3].
• Here, we report that the MHC class I-related neonatal Fc receptor (FcRn) is expressed within azurophilic and specific granules of neutrophils and relocates to phagolysosomes on phagocytosis of IgG-opsonized bacteria [4].
• The neonatal Fc receptor (FcRn) plays a critical role in regulating IgG homeostasis in vivo [5].
• The fact that Fcrn is a single copy gene indicates that it is expressed in both the neonatal intestine and the fetal yolk sac [6].

Biological context of Fcgrt

• 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 marsupial mammals [6].
• We report hat mice lacking the transporter associated with antigen presentation (TAP-/-) were also resistant to disease, whereas CD1-/- and CD8-/- mice were susceptible; susceptibility also did not correlate with neonatal Fc receptor or HEPH expression [7].
• Humanized IgG1 Variants with Differential Binding Properties to the Neonatal Fc Receptor: Relationship to Pharmacokinetics in Mice and Primates [8].

Anatomical context of Fcgrt

• Binding of NF1 protein to the Fcgrt promoter was confirmed in nuclear extracts of NIH3T3 cells and in adult mouse enterocytes, whereas an apparently different TF bound uniquely to the NF1 site in neonatal enterocyte extracts as the sole identified candidate for an expected developmental-specific high-level activator in this tissue [9].
• There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG across the intestinal epithelium of suckling mice [10].
• The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association [11].
• The neonatal Fc receptor, FcRn, is expressed in human placental syncytiotrophoblast, capillary endothelium, intestinal epithelium, and other tissues [12].
• IgG-assisted age-dependent clearance of Alzheimer's amyloid beta peptide by the blood-brain barrier neonatal Fc receptor [13].

Other interactions of Fcgrt

• The 5'-flanking region of the Fcrn gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL6 and NF1 [6].
• The studies indicate that the neonatal Fc receptor, FcRn, is involved in transcytosis across both yolk sac and neonatal intestine in addition to the regulation of IgG catabolism [14].

Analytical, diagnostic and therapeutic context of Fcgrt

• Sequence analysis of the Fcrn gene isolated from eight mouse strains showed that the membrane-distal domain of FcRn has at least three amino acid variants [6].
• Consistent with this result, Southern blot analysis with a mouse Fcrn cDNA probe detected cross-hybridizing bands in various mammalian species and chickens [6].

References