Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice.
A congenic, non-obese diabetic (NOD) mouse strain that contains a segment of chromosome 3 from the diabetes-resistant mouse strain B6.PL-Thy-1a was less susceptible to diabetes than NOD mice. A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), Fc gamma RI. The NOD Fcgr1 allele, which results in a deletion of the cytoplasmic tail, caused a 73 percent reduction in the turnover of cell surface receptor-antibody complexes. The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases.
Prins
J B
JB
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, United Kingdom.
Todd
J A
JA
Rodrigues
N R
NR
Ghosh
S
S
Hogarth
P M
PM
Wicker
L S
LS
Gaffney
E
E
Podolin
P L
PL
Fischer
P A
PA
Sirotina
A
A
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004705:Endocytosis; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D005819:Genetic Markers; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism
D005819:Genetic Markers; D007074:Immunoglobulin G; D017452:Receptors, IgG