Congenic mapping identifies a novel Idd9 subregion regulating type 1 diabetes in NOD mice

被引：2
作者：
Lin, Bixuan [1 ]
Ciecko, Ashley E. [1 ]
MacKinney, Erin [1 ,2 ]
Serreze, David V. [3 ]
Chen, Yi-Guang [1 ]
机构：
[1] Med Coll Wisconsin, Dept Pediat, Max McGee Natl Res Ctr Juvenile Diabet, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA
[2] Southern Illinois Univ, Sch Med, Springfield, IL 62702 USA
[3] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA
来源：
IMMUNOGENETICS | 2017年 / 69卷 / 03期
基金：
美国国家卫生研究院;
关键词：
Type; 1; diabetes; Idd9; Regulatory Tcells; NOD mouse; CD4(+)CD25(+) T-CELLS; DENDRITIC CELLS; SUSCEPTIBILITY; CONTRIBUTES; GENES; CD4; AUTOIMMUNITY; ASSOCIATION; CHILDREN; VARIANTS;
D O I：
10.1007/s00251-016-0957-3
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived Idd9 resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (Idd9.1, Idd9.2, Idd9.3, and Idd9.4) where B10-derived genes suppress T1D development in NOD mice. We independently generated and characterized six congenic strains containing B10-derived intervals that partially overlap with the Idd9.1 and Idd9.4 regions. T1D incidence studies have revealed a new B10-derived resistance region proximal to Idd9.1. Our results also indicated that a B10-derived gene(s) within the Idd9.4 region suppressed the diabetogenic activity of CD4 T cells and promoted CD103 expression on regulatory T cells indicative of an activated phenotype. In addition, we suggest the presence of a B10-derived susceptibility gene(s) in the Idd9.1/Idd9.4 region. These results provide additional information to improve our understanding of the complex genetic control by the Idd9 region.
引用
收藏
页码：193 / 198
页数：6
相关论文
共 39 条
  • [1] Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
    Barrett, Jeffrey C.
    Clayton, David G.
    Concannon, Patrick
    Akolkar, Beena
    Cooper, Jason D.
    Erlich, Henry A.
    Julier, Cecile
    Morahan, Grant
    Nerup, Jorn
    Nierras, Concepcion
    Plagnol, Vincent
    Pociot, Flemming
    Schuilenburg, Helen
    Smyth, Deborah J.
    Stevens, Helen
    Todd, John A.
    Walker, Neil M.
    Rich, Stephen S.
    [J]. NATURE GENETICS, 2009, 41 (06) : 703 - 707
  • [2] Identifying type 1 diabetes candidate genes by DNA microarray analysis of islet-specific CD4
    Berry, Gregory J.
    Frielle, Christine
    Brucklacher, Robert M.
    Salzberg, Anna C.
    Waldner, Hanspeter
    [J]. GENOMICS DATA, 2015, 5 : 184 - 188
  • [3] Regulatory T cells and inhibitory cytokines in autoimmunity
    Bettini, Maria
    Vignali, Dario A. A.
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2009, 21 (06) : 612 - 618
  • [4] Localization of Idd11 is not associated with thymus and NKT cell abnormalities in NOD mice
    Brodnicki, TC
    Fletcher, AL
    Pellicci, DG
    Berzins, SP
    McClive, P
    Quirk, F
    Webster, KE
    Scott, HS
    Boyd, RL
    Godfrey, DI
    Morahan, G
    [J]. DIABETES, 2005, 54 (12) : 3453 - 3457
  • [5] Genetic and functional association of the immune signaling molecule 4-1BB (CD137/TNFRSF9) with type 1 diabetes
    Cannons, JL
    Chamberlain, G
    Howson, J
    Smink, LJ
    Todd, JA
    Peterson, LB
    Wicker, LS
    Watts, TH
    [J]. JOURNAL OF AUTOIMMUNITY, 2005, 25 (01) : 13 - 20
  • [6] Molecular Signatures Differentiate Immune States in Type 1 Diabetic Families
    Chen, Yi-Guang
    Cabrera, Susanne M.
    Jia, Shuang
    Kaldunski, Mary L.
    Kramer, Joanna
    Cheong, Sami
    Geoffrey, Rhonda
    Roethle, Mark F.
    Woodliff, Jeffrey E.
    Greenbaum, Carla J.
    Wang, Xujing
    Hessner, Martin J.
    [J]. DIABETES, 2014, 63 (11) : 3960 - 3973
  • [7] Idd9/11 Genetic Locus Regulates Diabetogenic Activity of CD4 T-Cells in Nonobese Diabetic (NOD) Mice
    Chen, Yi-Guang
    Scheuplein, Felix
    Osborne, Melissa A.
    Tsaih, Shirng-Wern
    Chapman, Harold D.
    Serreze, David V.
    [J]. DIABETES, 2008, 57 (12) : 3273 - 3280
  • [8] ADOPTIVE TRANSFER OF DIABETES INTO IMMUNODEFICIENT NOD-SCID SCID MICE - RELATIVE CONTRIBUTIONS OF CD4+ AND CD8+ T-CELLS FROM DIABETIC VERSUS PREDIABETIC NOD.NON-THY-1A DONORS
    CHRISTIANSON, SW
    SHULTZ, LD
    LEITER, EH
    [J]. DIABETES, 1993, 42 (01) : 44 - 55
  • [9] The diabetes gene Zfp69 modulates hepatic insulin sensitivity in mice
    Chung, Bomee
    Stadion, Mandy
    Schulz, Nadja
    Jain, Deepak
    Scherneck, Stephan
    Joost, Hans-Georg
    Schuermann, Annette
    [J]. DIABETOLOGIA, 2015, 58 (10) : 2403 - 2413
  • [10] Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes
    Diana, Julien
    Simoni, Yannick
    Furio, Laetitia
    Beaudoin, Lucie
    Agerberth, Birgitta
    Barrat, Franck
    Lehuen, Agnes
    [J]. NATURE MEDICINE, 2013, 19 (01) : 65 - 73
1234