title: Centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1 diabetes in NOD.CD72b congenic mice.
abstract: The nonobese diabetic (NOD) mouse is a useful model of autoimmune type 1 diabetes exhibiting many similarities to human type 1 diabetes patients including the presence of auto-reactive T cells and pancreas-specific autoantiboies. Multiple Idd loci control the development of diabetes in NOD mice. CD72, a B cell membrane-bound glycoprotein carrying a C-type lectin-like domain, is an inhibitory co-receptor of the B cell antigen receptor (BCR) that negatively regulates BCR signaling. Among four known haplotypes of mouse CD72, NOD mice carry the CD72(c) haplotype, whereas most of the other inbred strains of mice carry either CD72(a) or CD72(b). In this study, we generated congenic NOD.CD72(b) mice that carry C57BL/6 (B6) mouse-derived centromeric chromosome 4 interval (24-45cM) surrounding the CD72(b) locus. Unexpectedly, NOD.CD72(b) mice were not protected from diabetes, but rather exhibited accelerated development of both insulitis and diabetes. Our result defines novel locus or loci in the vicinity of CD72 gene that negatively control diabetes, indicating that NOD disease is under complex genetic controls of not only Idd genes but also disease-resistant genes.
authors.affiliation: Laboratory of Immunology, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Rong
authors.initials: R
authors.lastname: Hou
authors.forename: Mareki
authors.initials: M
authors.lastname: Ohtsuji
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohtsuji
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Adachi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009077:Mucins / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D009077:Mucins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse