Reduced galactosyltransferase mRNA levels are associated with the agalactosyl IgG found in arthritis-prone MRL-lpr/lpr strain mice.
MRL-lpr/lpr strain mice have defectively glycosylated IgG. This may be related to the rheumatoid arthritis (RA)-like disease that occurs in these mice, because a similar glycosylation defect is seen in human subjects with RA. Whilst it is known that this defect is associated with reduced activity of the beta-1,4-galactosyltransferase (beta-1,4-GalTase) enzyme, the cause of this reduced activity is at present unknown. We have therefore examined the molecular genetics of beta-1,4-GalTase in MRL-lpr/lpr mice. Using 10 different restriction endonucleases we found no evidence for a polymorphic variant of the gene in glycosylation-defective mice. However, the level of mRNA for beta-1,4-GalTase was lowest in the MRL-lpr/lpr mice, the strain with the most poorly galactosylated IgG of the four strains examined. Thus, the reduced level of IgG oligosaccharide galactosylation found in MRL-lpr/lpr strain mice appears to be related to either an altered transcriptional level of, or altered mRNA stability for, beta-1,4-GalTase in lymphocytes from these mice.
Department of Immunology, University College London Medical School, UK.
P A
PA
Jeddi
T
T
Lund
K B
KB
Bodman
N
N
Sumar
P M
PM
Lydyard
L
L
Pouncey
L S
LS
Heath
V J
VJ
Kidd
P J
PJ
Delves
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D015139:Blotting, Southern; D005700:Galactosyltransferases / Q000235:genetics*; D005821:Genetic Techniques; D006031:Glycosylation; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity
D007074:Immunoglobulin G; D012333:RNA, Messenger; D005700:Galactosyltransferases