CRISPR-Cas9-Mediated Modification of the NOD Mouse Genome With Ptpn22R619W Mutation Increases Autoimmune Diabetes

被引：29

作者：

Lin, Xiaotian ^{[1
]}

Pelletier, Stephane ^{[2
]}

Gingras, Sebastien ^{[2
,3
]}

Rigaud, Stephanie ^{[1
]}

Maine, Christian J. ^{[1
]}

Marquardt, Kristi ^{[1
]}

Dai, Yang D. ^{[1
]}

Sauer, Karsten ^{[1
]}

Rodriguez, Alberto R. ^{[4
]}

Martin, Greg ^{[4
]}

Kupriyanov, Sergey ^{[4
]}

Jiang, Ling ^{[5
]}

Yu, Liping ^{[5
]}

Green, Douglas R. ^{[2
]}

Sherman, Linda A. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[2] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA

[3] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA

[4] Scripps Res Inst, Murine Genet Core, La Jolla, CA 92037 USA

[5] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

来源：

DIABETES | 2016年 / 65卷 / 08期

基金：

美国国家卫生研究院;

关键词：

OF-FUNCTION VARIANT; ONE-STEP GENERATION; TYROSINE PHOSPHATASE; DISEASE; MICE; AUTOANTIBODIES; SUSCEPTIBILITY; MODEL;

D O I：

10.2337/db16-0061

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

An allelic variant of protein tyrosine phosphatase non-receptor type 22 (PTPN22), PTPN22(R620W), is strongly associated with type 1 diabetes (T1D) in humans and increases the risk of T1D by two-to fourfold. The NOD mouse is a spontaneous T1D model that shares with humans many genetic pathways contributing to T1D. We hypothesized that the introduction of the murine orthologous Ptpn22(R619W) mutation to the NOD genome would enhance the spontaneous development of T1D. We microinjected CRISPR-Cas9 and a homology-directed repair template into NOD single-cell zygotes to introduce the Ptpn22(R619W) mutation to its endogenous locus. The resulting Ptpn22(R619W) mice showed increased insulin autoantibodies and earlier onset and higher penetrance of T1D. This is the first report demonstrating enhanced T1D in a mouse modeling human PTPN22(R620W) and the utility of CRISPR-Cas9 for direct genetic alternation of NOD mice.

引用

页码：2134 / 2138

页数：5

共 25 条

[1] Tyrosine Phosphatase PTPN22: Multifunctional Regulator of Immune Signaling, Development, and Disease
Bottini, Nunzio
Peterson, Erik J.
[J]. ANNUAL REVIEW OF IMMUNOLOGY, VOL 32, 2014, 32 : 83 - 119
[2] Gene Targeting in NOD Mouse Embryos Using Zinc-Finger Nucleases
Chen, Yi-Guang
Forsberg, Matthew H.
Khaja, Shamim
Ciecko, Ashley E.
Hessner, Martin J.
Geurts, Aron M.
[J]. DIABETES, 2014, 63 (01) : 68 - 74
[3] Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, Le
Ran, F. Ann
Cox, David
Lin, Shuailiang
Barretto, Robert
Habib, Naomi
Hsu, Patrick D.
Wu, Xuebing
Jiang, Wenyan
Marraffini, Luciano A.
Zhang, Feng
[J]. SCIENCE, 2013, 339 (6121) : 819 - 823
[4] A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models
Dai, Xuezhi
James, Richard G.
Habib, Tania
Singh, Swati
Jackson, Shaun
Khim, Socheath
Moon, Randall T.
Liggitt, Denny
Wolf-Yadlin, Alejandro
Buckner, Jane H.
Rawlings, David J.
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (05) : 2024 - 2036
[5] Themis sets the signal threshold for positive and negative selection in T-cell development
Fu, Guo
Casas, Javier
Rigaud, Stephanie
Rybakin, Vasily
Lambolez, Florence
Brzostek, Joanna
Hoerter, John A. H.
Paster, Wolfgang
Acuto, Oreste
Cheroutre, Hilde
Sauer, Karsten
Gascoigne, Nicholas R. J.
[J]. NATURE, 2013, 504 (7480) : 441 - +
[6] PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells
Hasegawa, K
Martin, F
Huang, GM
Tumas, D
Diehl, L
Chan, AC
[J]. SCIENCE, 2004, 303 (5658) : 685 - 689
[7] A SNP in the Immunoregulatory Molecule CTLA-4 Controls mRNA Splicing In Vivo but Does Not Alter Diabetes Susceptibility in the NOD Mouse
Jakubczik, Fabian
Jones, Ken
Nichols, Jennifer
Mansfield, William
Cooke, Anne
Holmes, Nick
[J]. DIABETES, 2016, 65 (01) : 120 - 128
[8] Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease
Lempainen, Johanna
Laine, Antti-Pekka
Hammais, Anna
Toppari, Jorma
Simell, Olli
Veijola, Riitta
Knip, Mikael
Ilonen, Jorma
[J]. JOURNAL OF AUTOIMMUNITY, 2015, 61 : 45 - 53
[9] Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology
Li, Feng
Cowley, Dale O.
Banner, Debra
Holle, Eric
Zhang, Liguo
Su, Lishan
[J]. SCIENTIFIC REPORTS, 2014, 4
[10] RNA-Guided Human Genome Engineering via Cas9
Mali, Prashant
Yang, Luhan
Esvelt, Kevin M.
Aach, John
Guell, Marc
DiCarlo, James E.
Norville, Julie E.
Church, George M.
[J]. SCIENCE, 2013, 339 (6121) : 823 - 826

← 1 2 3 →