Seigo Terawaki
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,
   Position   Assistant Professor with Special Assignment
Article types 原著
Language English
Peer review Peer reviewed
Title Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice.
Journal Formal name：International immunology
Abbreviation：Int Immunol
ISSN code：14602377/09538178
Domestic / ForeginForegin
Volume, Issue, Page 21(5),pp.499-509
Author and coauthor Jiang Fang, Yoshida Taku, Nakaki Fumio, Terawaki Seigo, Chikuma Shunsuke, Kato Yu, Okazaki Il-Mi, Honjo Tasuku, Okazaki Taku
Publication date 2009/05
Summary The non-obese diabetic (NOD) mouse strain is prone to developing various autoimmune syndromes including type I diabetes mellitus (T1DM), sialadenitis, thyroiditis and pancreatitis. Although the genetic basis of T1DM has been extensively analyzed, genetic factors that modify the other autoimmune phenotypes are largely unknown. We have recently reported that NOD mice with anti-diabetogenic MHC haplotype (H-2(b)) and programmed cell death 1 (PD-1) deficiency (NOD.H2(b)-Pdcd1(-/-) mice) are protected from T1DM but develop various tissue-specific autoimmune diseases including peripheral neuropathy due to autoimmune neuritis, sialadenitis and gastritis. In the present study, we generated [(C57BL/6 x NOD.H2(b))(F1) x NOD-H2(b)](BC1)-Pdcd1(-/-) mice to screen non-MHC quantitative trait loci (QTLs) that modify autoimmune phenotypes other than T1DM. We identified seven QTLs for peripheral neuropathy and neuritis, one QTL for insulitis, four QTLs for gastritis, two QTLs for sialadenitis and seven QTLs for vasculitis throughout the genome and designated them as Annp loci for autoimmunity due to polymorphisms of non-MHC genes in NOD mice and PD-1 deficiency. Annp1, 5, 6 and 7 overlapped with reported loci for T1DM (Idd3, 9, 15 and 2, respectively), suggesting that these loci modify not only T1DM but also other autoimmune phenotypes. NOD allele was promotive at 9 of 14 Annp loci, while NOD allele was protective at the other loci. Half of Annp loci associated with a single phenotype, while the other seven loci associated with more than two phenotypes. These results indicate that NOD genetic background harbors various QTLs that modify autoimmune phenotypes either by organ-specific or by organ-non-specific manner.
DOI 10.1093/intimm/dxp020
PMID 19261693