Extracellular mutations of non-obese diabetic mouse Fc gamma RI modify surface expression and ligand binding

The non-obese diabetic mouse (NOD) expresses a unique form of the high affinity receptor for IBG (Fc gamma RI), containing multiple mutations that result in substitutions and insertions of amino acids and a truncated cytoplasmic tail, As a result of these major changes, receptor affinity for IgG increases 10-fold over that of wild-type Fc gamma RI from BALB/c mice, while the specificity for ligand is retained, Kinetic analysis revealed that while the association rate of IgG with Fc gamma RI from NOD mice (Fc gamma RI-NOD) and Fc gamma RI from BALB/c mice (Fc gamma RI-BALB) is similar, IgG bound much more tightly to Fc gamma RI-NOD as revealed by a profoundly diminished dissociation rate. Transfection studies demonstrated that Fc gamma RI-NOD was expressed at one-tenth of the level of Fc gamma RI-BALB, Although mouse Fc gamma RI was previously not known to associate with the Fc epsilon RI gamma-subunit, transfection of COS-7 cells demonstrates that like human Fc gamma RI, mouse Fc gamma RI is also able to associate with this signaling subunit. Furthermore, expression levels of Fc gamma RI-NOD were not restored by the presence of the Fc epsilon RI gamma-subunit, The difference in the levels of expression was mapped to mutations in the extracellular region of Fc gamma RI-NOD as replacement of the extracellular domains with those of human Fc gamma RI or Fc gamma RI-BALB restored expression to that of human Fc gamma RI or Fc gamma RI-BALB.