品系特点
原始参考文献
Info 当使用该小鼠品系发表文献时,请引用原始文献,并在材料方法中提供该品系的品系货号:JAX stock#001976
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品系详情
NOD/ShiLtJ 小鼠的糖尿病表现为胰岛炎(胰岛可见白细胞浸润)。雌鼠在约 12 周龄时出现胰腺胰岛素含量显著降低,该现象在雄鼠中发生时间要晚数周。糖尿病发病指标为中度糖尿,以及非空腹血糖高于 250 mg/dL。糖尿病小鼠具有低胰岛素血症和高胰高血糖素血症,提示胰岛 β 细胞有选择性功能损伤。NOD/ShiLtJ 小鼠对 IDDM 的易感性是多基因共同影响的结果,同时环境(包括笼养条件、健康状况和饲料)对外显率也有较强影响。NOD/ShiLtJ 雌鼠比雄鼠的应用更广,因为雌鼠的 IDDM 症状发作时间更早,发病率更高(30 周龄时达 90-100%)。NOD/ShiLtJ 雄鼠在 30-40 周龄时的 IDDM 发病率仅 40-60%。不过,雄鼠也有很大用途,包括药物研究、IDDM“加速转运”和一些体外研究。造成 NOD 小鼠对糖尿病易感的主要原因是其特有的 MHC 单体型(H2g7 = Kd、Aad、Abg7、Enull、Db)。NOD 小鼠还具有多种异常免疫表型表现,包括抗原呈递细胞免疫调节功能缺陷、T 淋巴细胞库调节功能缺陷、NK 细胞功能缺陷、巨噬细胞细胞因子分泌缺陷 (Fan et al., 2004) 以及伤口愈合能力受损。此品系小鼠也缺乏溶血补体 C5。此外,NOD/ShiLtJ 小鼠的听力也严重受损。多种致免疫缺陷突变、细胞因子基因靶向突变以及影响免疫功能的转基因,均已回交至 NOD/ShiLt 近交系背景。
品系建立
NOD 近交小鼠最早由 Shionogi 白内障 (Cataract Shionogi, CTS) 品系小鼠近交繁殖获得,CTS 小鼠来自于远交系 Jcl:ICR 小鼠。繁殖到 F6 代时,取非白内障、高空腹血糖水平小鼠继续与 NOD/Shi 小鼠祖先进行近交。在 F13 代时,从目前的 NON/Shi 品系分离出 NOD 祖先。虽然高空腹血糖水平仍然是后代品系的选择依据,但 F13 及其后代的 NOD 祖先是根据正常空腹血糖水平选择的。1974 年,繁殖到 F20 代时,“血糖正常”品系雌鼠自发出现明显的胰岛素依赖型糖尿病 (insulin-dependent diabetes mellitus, IDDM) 伴胰岛炎症状。选择性育种此糖尿病雌性后代获得了非肥胖型糖尿病 (nonobese diabetic, NOD) 品系。NOD 亚系最初仅限在日本销售,20 世纪 80 年代初才引入澳大利亚和美国销售。1984 年,M. Hattori 博士将 NOD 和 NON 品系从日本京都的一个小鼠种群引进到波士顿的加斯林糖尿病中心。此次引进的繁育对从加斯林糖尿病中心转呈给杰克森实验室的 E Leiter 博士,成为 NOD/ShiLtJ 和 NON/ShiLtJ 生产品系的小鼠来源。
参考文献
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当使用该小鼠品系发表文献时,请引用原始文献,并在材料方法中提供该品系的品系货号:JAX stock#001976


2019

Therapeutic administration of Tregitope-Human Albumin Fusion with Insulin Peptides to promote Antigen-Specific Adaptive Tolerance Induction.

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PubMed:31695065

MGI:J:281351

Sci Rep 9(1):16103

2017

Complete overview of protein-inactivating sequence variations in 36 sequenced mouse inbred strains.

Timmermans S , et al.

PubMed:28784771

MGI:J:244295

Proc Natl Acad Sci U S A 114(34):9158-9163

2015

Genetic Analysis of Substrain Divergence in Non-Obese Diabetic (NOD) Mice.

Simecek P , et al.

PubMed:25740934

MGI:J:257336

G3 (Bethesda) 5(5):771-5

1997

Initiation of autoimmune diabetes in NOD/Lt mice is MHC class I-dependent.

Serreze DV , et al.

PubMed:9103469
MGI:J:39473
J Immunol 158(8):3978-86
1993

The NOD mouse: A model for analyzing the interplay between heredity and environment in development of autoimmune disease.

Leiter EH , et al.

PubMed:
MGI:J:12784
ILAR News 35(1):4-14
1980

Breeding of a non-obese, diabetic strain of mice.

Makino S , et al.

PubMed:6995140
MGI:J:25411
Jikken Dobutsu 29(1):1-13
其它参考文献
2016

Unstable FoxP3+ T regulatory cells in NZW mice.

Depis F , et al.

PubMed:26768846
MGI:J:227903
Proc Natl Acad Sci U S A 113(5):1345-50
2011

Mouse genomic variation and its effect on phenotypes and gene regulation.

Keane TM , et al.

PubMed:21921910
MGI:J:177037
Nature 477(7364):289-94
2008

Social approach and repetitive behavior in eleven inbred mouse strains.

Moy SS , et al.

PubMed:18440079
MGI:J:138681
Behav Brain Res 191(1):118-29
2004

Development of a SNP genotyping panel for genetic monitoring of the laboratory mouse.

Petkov PM , et al.

PubMed:15081119
MGI:J:89298
Genomics 83(5):902-11
2004

Strain distribution pattern of susceptibility to immune-mediated nephritis.

Xie C , et al.

PubMed:15067087
MGI:J:122988
J Immunol 172(8):5047-55
2003

Adenovirus early region 3 antiapoptotic 10.4K, 14.5K, and 14.7K genes decrease the incidence of autoimmune diabetes in NOD mice.

Pierce MA , et al.

PubMed:12716741
MGI:J:83195
Diabetes 52(5):1119-27
2002

During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities.

DiLorenzo TP , et al.

PubMed:12498815
MGI:J:94192
Clin Immunol 105(3):332-41
2001

Cytotoxic T lymphocyte and cDNA sequence analyses of the MHC class Ib molecule Qa1 in nonobese diabetic mice.

Chun T , et al.

PubMed:11685462
MGI:J:72438
Immunogenetics 53(6):506-10
2001

Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation.

Nagy A , et al.

PubMed:11522677
MGI:J:71049
Diabetes 50(9):2100-4
2001

Autoantibody Patterns in Diabetes-prone NOD Mice and in Standard C57BL/6 Mice.

Quintana FJ , et al.

PubMed:11712856
MGI:J:72893
J Autoimmun 17(3):191-7
2001

Il-12 administration reveals diabetogenic t cells in genetically resistant i-ealpha-transgenic nonobese diabetic mice: resistance to autoimmune diabetes is associated with binding of ealpha-derived peptides to the i-a(g7) molecule.

Trembleau S , et al.

PubMed:11712856
MGI:J:72893
J Autoimmun 17(3):191-7
2000

Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice.

Serreze DV , et al.

PubMed:11118001
MGI:J:65986
Diabetes 49(12):2007-11
1998

NOD Mice and Related Strains: Origins, Husbandry and Biology Introduction

Leiter EH , et al.

1997

Apoptosis is increased in a model of diabetes-impaired wound healing in genetically diabetic mice.

Darby IA , et al.

PubMed:9076954
MGI:J:40898
Int J Biochem Cell Biol 29(1):191-200
1995

Studies on the polymorphism of the fifth component of complement in laboratory mice.

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PubMed:8919358
MGI:J:31912
Exp Clin Immunogenet 12(4):253-60
1994

Prevention of diabetes in the NOD mouse: implications for therapeutic intervention in human disease.

Bowman MA , et al.

PubMed:8172643
MGI:J:17091
Immunol Today 15(3):115-20
1994

Genetic and pathogenic basis of autoimmune diabetes in NOD mice.

Serreze DV , et al.

PubMed:7710714
MGI:J:22216
Curr Opin Immunol 6(6):900-6
等位基因参考文献
基因分型和繁育
近似对照
ICR/HaJ                              NOD.129S7(B6)-Rag1tm1Mom/J              
NOD.B10Sn-H2b/J               NOD.Cg-Prkdcscid/J               
小鼠在离乳时经爪垫接种弗氏完全佐剂 (Complete Freunds Adjuvant, CFA) 将延迟糖尿病发病时间,从而延长繁育对寿命。关于弗氏完全佐剂在 NOD 小鼠中应用的讨论,请参阅《现行免疫学方案》(Current Protocols in Immunology) 第 15.9.1-15.9.23 页(参见免疫学方案下方的 PDF 链接)。
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