M-NSG

品系全名

NOD.Cg-PrkdcscidIl2rgem1Smoc

目录号

NM-NSG-001

品系状态

活体

导出PDF

基因信息

基因名
IL2RG

品系描述

NOD背景下Prkdc纯合突变:Prkdc(protein kinase, DNA-activated, catalytic polypeptide)基因主要编码DNA依赖性蛋白激酶(DNA-PK)的催化亚基,是参与双链DNA断裂修复、免疫球蛋白和T细胞受体可变(V)、多样性(D)、连接(J)区段重组的重要基因。Prkdcscid突变代表严重的联合免疫缺陷,表现为缺失T、B细胞,无法介导细胞和体液免疫,不排斥同种和异种移植。无功能T细胞和B细胞,NK细胞活性低,没有溶血补体活性,骨髓发育缺陷。血清免疫球蛋白(Ig)泄漏率非常低,非常适合同种和异种肿瘤移植。 IL2rgnull突变:Interleukin-2受体gamma链(IL-2Rγc,又称CD132)是具有重要免疫功能的细胞因子Il2、Il-4、Il-7、Il-9、Il-15和Il-21的共同受体亚基,该基因敲除后的小鼠机体免疫功能严重降低,通过多种受体阻断细胞因子信号传导,导致功能性NK细胞缺陷。 M-NSG严重免疫缺陷小鼠,缺失成熟T、B、NK细胞,可高效地植入人CD34+造血干细胞(HSC)、外周血单核细胞(PBMC)、病人来源异种移植物(PDX)或成体干细胞和组织,基本上可以植入人体免疫系统,是研究人体免疫功能,传染病,糖尿病,肿瘤学和干细胞生物学的重要免疫缺陷小鼠,是目前国际公认的免疫缺陷程度较高、较适合人源细胞或组织移植的工具小鼠。
应用领域:免疫及造血系统研究,肿瘤或细胞移植等。

验证数据

表型分析

T、B、NK 细胞 FACS 检测

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图 1.M-NSG 小鼠脾脏中 T、B 和 NK 细胞缺失。取 BALB/c、NOD-scid 和 M-NSG 小鼠的脾脏细胞,通过 FACS 对其中 T、B 和 NK 细胞的组成进行分析 (A) 并进行统计对比 (B)


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图 2.M-NSG 小鼠血液中 T、B 和 NK 细胞缺失。取 BALB/c、NOD-scid 和 M-NSG 小鼠的外周血,通过 FACS 对其中 T、B 和 NK 细胞的组成进行分析 (A) 并进行统计对比 (B)


M、MΦ、DC 细胞 FACS 检测

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图 3.M-NSG 小鼠脾脏中单核细胞、巨噬细胞和 DC 细胞比例。取 BALB/c、NOD-scid 和 M-NSG 小鼠的脾脏细胞,通过 FACS 对其中单核细胞、巨噬细胞和 DC 细胞的组成进行分析 (A) 并进行统计对比 (B)


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图 4.M-NSG 小鼠外周血中单核细胞、巨噬细胞和 DC 细胞比例。取 BALB/c、NOD-scid 和 M-NSG 小鼠的外周血,通过 FACS 对其中单核细胞、巨噬细胞和 DC 细胞的组成进行分析 (A) 并进行统计对比 (B)


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图5. M-NSG小鼠生长曲线(n=600)


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图6. M-NSG小鼠血清抗体亚类检测(雄性,8周龄)。


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图7. M-NSG 各组织病理学检测。A:除脾脏和胸腺外,其他组织未见明显异常,包括:脑、视网膜、脊髓、心脏、肝、肺、肾、小肠、大肠、胃、唾液腺、胰腺、卵巢、子宫、睾丸、附睾、骨骼肌、皮肤和棕色脂肪(雌性,6周龄);B,C: M-NSG小鼠的脾脏缺乏白髓,淋巴细胞减少(6周龄)。


表1. M-NSG小鼠血常规检测

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表2. M-NSG小鼠血生化检测

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CDX/PDX成瘤及药效验证

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图8. A549 肺肿瘤细胞(A)或 Raji 淋巴瘤细胞(B)在 M-NSG 小鼠上的成瘤验证。


基于 M-NSG 小鼠成功建立的 CDX 模型image.png


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图9.利用淋巴癌(Raji)CDX模型进行抗人CD47抗体药效验证实验。


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图10. 利用肺癌(A549)CDX模型进行CAR-T药效验证实验。

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图11. 移植CAR-T的M-NSG小鼠体内的GVHD研究。


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图12. 肝癌PDX在 M-NSG 小鼠上的成瘤验证。


人源免疫系统重建模型 

利用重度免疫缺陷M-NSG小鼠可以通过移植人源外周血细胞、造血干细胞等,实现在小鼠体内重塑人源免疫系统,为免疫学、肿瘤学及人类传染疾病等研究提供有力工具。


PBMC人源化小鼠

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Hu-PBMC模型,或者被称为Hu-PBL(perihperal blood lymphocyte, PBL)模型,是一种构建较为简单和经济的免疫系统人源化小鼠模型。Hu-PBMC模型的移植方式主要有腹腔注射与尾静脉注射,通常以4-6周龄的M-NSG小鼠作为移植受体,PBMC移植/接种量通常在5~10*10^6/小鼠。该模型常被用于研究人效应T细胞的活化以及评估免疫抑制药物。


Hu-PBMC模型的供体筛选


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图13.  M-NSG小鼠中进行Hu-PBMC重建的供体筛选。


image.png图14.流式分析Hu-PBMC模型外周血淋巴细胞亚群。将人PBMCs(5E6)静脉注射M-NSG小鼠(雌性,6-8周龄,n=4)。植入human PBMCs后取不同时间点的小鼠血液进行流式细胞分析。


image.png图15. 利用骨髓瘤(H929)Hu-PBMC模型进行体内药效研究。


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图16. 利用乳腺癌(MDA-MB-231)Hu-PBMC模型进行体内药效研究。


HSC人源化小鼠

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Hu-HSC模型,也叫hu-CD34+,或叫hu-SRC(scid-repopulatingcell),已经被广泛应用于研究人类造血发育、细胞介导的免疫反应以及HIV和EBV等病毒感染性疾病中。 其构建方式是将来自人脐带血、骨髓、G-CSF激活的外周血或胎肝的人CD34+ HSCs通过静脉内(i.v.)或股骨内(i.f.)注射到成年免疫缺陷小鼠M-NSG中,得到的小鼠可以产生多种造血干细胞。image.png


图17. M-NSG小鼠中进行Hu-HSC重建的供体筛选。

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图18. 流式分析Hu-HSC模型外周血淋巴细胞亚群。


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图19. 利用乳腺癌(MDA-MB-231)Hu-HSC模型进行体内药效研究。


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97. Sequence-based drug design as a concept in computational drug design
发表年份:2023 来源杂志:Nature Communications

98. TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models
发表年份:2023 来源杂志:Nature Communications

99. Low level of ARID1A contributes to adaptive immune resistance and sensitizes triple-negative breast cancer to immune checkpoint inhibitors
发表年份:2023 来源杂志:Cancer Communications

100. Enhancement of CAR-T cell activity against cholangiocarcinoma by simultaneous knockdown of six inhibitory membrane proteins
发表年份:2023 来源杂志:Cancer Communications

101. Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling
发表年份:2023 来源杂志:JOURNAL OF CLINICAL INVESTIGATION

102. Cell autonomous expression of BCL6 is required to maintain lineage identity of mouse CCR6+ ILC3s
发表年份:2023 来源杂志:JOURNAL OF EXPERIMENTAL MEDICINE

103. CAR-Aptamers Enable Traceless Enrichment and Monitoring of CAR-Positive Cells and Overcome Tumor Immune Escape
发表年份:2023 来源杂志:Advanced Science

104. NIRF/PET imaging of γδ T cells via metabolic glycoengineering and bioorthogonal labeling
发表年份:2023 来源杂志:CHEMICAL ENGINEERING JOURNAL

105. Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq
发表年份:2023 来源杂志:Advanced Science

106. Targeted therapy of central nervous system acute lymphoblastic leukemia with an integrin α6-targeted self-assembling proapoptotic nanopeptide
发表年份:2023 来源杂志:Engineering

107. Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4β7-integrin therapy in humanized mice with colitis
发表年份:2023 来源杂志:Gut Microbes

108. Transcription factor Nkx2-3 maintains the self-renewal of hematopoietic stem cells by regulating mitophagy
发表年份:2023 来源杂志:LEUKEMIA

109. TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability
发表年份:2023 来源杂志:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

110. Targeting the Immunoglobulin IGSF9 Enhances Antitumor T-cell Activity and Sensitivity to Anti–PD-1 Immunotherapy
发表年份:2023 来源杂志:CANCER RESEARCH

111. PICH activates Cyclin A1 transcription to drive S-phase progression and chemoresistance in gastric cancer.
发表年份:2023 来源杂志:CANCER RESEARCH

112. Faecalibacterium prausnitzii abrogates intestinal toxicity and promotes tumor immunity to increase the efficacy of dual CTLA-4 and PD-1 checkpoint blockade
发表年份:2023 来源杂志:CANCER RESEARCH

113. Targeted glycan degradation potentiates cellular immunotherapy for solid tumors
发表年份:2023 来源杂志:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

114. Sitravatinib as a potent FLT3 inhibitor can overcome gilteritinib resistance in acute myeloid leukemia
发表年份:2023 来源杂志:Biomarker Research

115. TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer
发表年份:2023 来源杂志:JOURNAL OF NANOBIOTECHNOLOGY

116. DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response
发表年份:2023 来源杂志:HAEMATOLOGICA

117. T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies
发表年份:2022-07-26 来源杂志:nature communications

118. A Chimeric Conjugate of Antibody and Programmable DNA Nanoassembly Smartly Activates T cell for Precise Cancer Cell Targeting
发表年份:2022-06-24 来源杂志:A Journal of the Gesellschaft Deutscher Chemiker

119. BSA-AIE Nanoparticles with Boosted ROS Generation for Immunogenic Cell Death Immunotherapy of Multiple Myeloma
发表年份:2022 来源杂志:ADVANCED MATERIALS

120. Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy
发表年份:2022 来源杂志:Nature Biomedical Engineering

121. T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies
发表年份:2022 来源杂志:Nature Communications

122. Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica
发表年份:2022 来源杂志:Nature Communications

123. Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture
发表年份:2022 来源杂志:Advanced Science

124. Inhibition of Calcium Signaling Prevents Exhaustion and Enhances Anti-Leukemia Efficacy of CAR-T Cells via SOCE-Calcineurin-NFAT and Glycolysis Pathways
发表年份:2022 来源杂志:Advanced Science

125. Nano-Biohybrid DNA Engager That Reprograms the T-Cell Receptor
发表年份:2022 来源杂志:Journal of the American Chemical Society

126. Therapeutic strategies targeting uPAR potentiate anti–PD-1 efficacy in diffuse-type gastric cancer
发表年份:2022 来源杂志:Science Advances

127. Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia
发表年份:2022 来源杂志:Acta Pharmaceutica Sinica B

128. An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ
发表年份:2022 来源杂志:MOLECULAR THERAPY

129. Single-cell ATAC-seq maps the comprehensive and dynamic chromatin accessibility landscape of CAR-T cell dysfunction
发表年份:2022 来源杂志:LEUKEMIA

130. FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer
发表年份:2022 来源杂志:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

131. Deneddylation of PML/RARα reconstructs functional PML nuclear bodies via orchestrating phase separation to eradicate APL
发表年份:2022 来源杂志:CELL DEATH AND DIFFERENTIATION

132. Visualizing γδ T cells by very late antigen-4-targeted positron emission tomography
发表年份:2022 来源杂志:EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING

133. Chemokine Receptor CCR2b Enhanced Anti-tumor Function of Chimeric Antigen Receptor T Cells Targeting Mesothelin in a Non-small-cell Lung Carcinoma Model
发表年份:2021-03-11 来源杂志:Front. Immunol

134. Bcl-2 Enhances Chimeric Antigen Receptor T Cell Persistence by Reducing Activation-Induced Apoptosis
发表年份:2021-01-08 来源杂志:Cancers

135. Liver type 1 innate lymphoid cells develop locally via an interferon-γ–dependent loop
发表年份:2021 来源杂志:SCIENCE

136. A chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity
发表年份:2021 来源杂志:Science Translational Medicine

137. The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability
发表年份:2021 来源杂志:MOLECULAR CELL

138. CAFs shape myeloid-derived suppressor cells to promote stemness of intrahepatic cholangiocarcinoma through 5-lipoxygenase
发表年份:2021 来源杂志:HEPATOLOGY

139. DMDRMR-Mediated Regulation of m6A-Modified CDK4 by m6A Reader IGF2BP3 Drives ccRCC Progression
发表年份:2021 来源杂志:CANCER RESEARCH

140. Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
发表年份:2021 来源杂志:CLINICAL CANCER RESEARCH

141. WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit
发表年份:2021 来源杂志:Acta Pharmaceutica Sinica B

142. TIGIT-Fc Promotes Antitumor Immunity
发表年份:2021 来源杂志:Cancer Immunology Research

143. 4-1BB Signaling Boosts the Anti-Tumor Activity of CD28-Incorporated 2nd Generation Chimeric Antigen Receptor-Modified T Cells
发表年份:2020-11-13 来源杂志:Frontiers in Immunology

144. SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation
发表年份:2020-05-19 来源杂志:NAT COMMUN

145. Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus
发表年份:2019-05-01 来源杂志:J Biomed Nanotechnol

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