Jeddi P A, Lund T, Bodman K B, Sumar N, Lydyard P M, Pouncey L, Heath L S, Kidd V J, Delves P J
Department of Immunology, University College London Medical School, UK.
Immunology. 1994 Nov;83(3):484-8.
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.
MRL-lpr/lpr品系小鼠存在糖基化缺陷的免疫球蛋白G（IgG）。这可能与这些小鼠中出现的类风湿关节炎（RA）样疾病有关，因为在患RA的人类受试者中也观察到类似的糖基化缺陷。虽然已知这种缺陷与β-1,4-半乳糖基转移酶（β-1,4-GalTase）活性降低有关，但目前尚不清楚这种活性降低的原因。因此，我们研究了MRL-lpr/lpr小鼠中β-1,4-GalTase的分子遗传学。使用10种不同的限制性内切酶，我们在糖基化缺陷小鼠中未发现该基因存在多态性变体的证据。然而，在所检测的四个品系中，MRL-lpr/lpr小鼠中β-1,4-GalTase的mRNA水平最低，该品系的IgG糖基化程度最差。因此，MRL-lpr/lpr品系小鼠中发现的IgG寡糖半乳糖基化水平降低似乎与这些小鼠淋巴细胞中β-1,4-GalTase的转录水平改变或mRNA稳定性改变有关。
