Kras-LSL-G12D

品系全名

C57BL/6JSmo-Krasem4(LSL-G12D)Smoc

目录号

NM-KI-190003

品系状态

活体

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基因信息

基因名
Kras

品系描述

野生型Kras激活/失活效应是受控的,而突变型Kras蛋白功能异常,持续处于激活状态,导致肿瘤细胞的持续增殖。将loxp-stop-loxp以及含有G12D的exon2替换Kras的exon2,建立Kras基因G12D条件性点突变小鼠品系,该小鼠与Cre小鼠交配后可获得G12D点突变小鼠。Kras(LSL-G12D/LSL-G12D);纯合子胚胎期即发生死亡。
应用领域:肿瘤研究

验证数据

Kras-(LSL-G12D)-1.png图1. 采用气管内注射的方法,将AAV-cre病毒注射到小鼠肺部,3个月后对小鼠肺部进行CT检测,CT结果显示有明显的肿瘤的形成。

image.png

图2. Scgb1a1CreERT2/+; KrasG12D/+小鼠肺部CT检测结果。小鼠经腹腔注射玉米油/他莫西芬5次,5个月后对其肺部进行CT检测。

image.png

图3. Scgb1a1CreERT2/+; KrasG12D/+小鼠肺组织的H&E染色结果。肺部肿瘤均为肺腺癌,黑色箭头指示肿瘤组织。 Grade I和Grade IV :动物肿瘤分级。


此外,我们还可以提供Kras(LSL-G12D/+)小鼠肿瘤细胞来源的荷瘤小鼠模型。肿瘤细胞可在受体小鼠体内快速增殖(如图2)。荷瘤小鼠模型可提高临床药效评价实验操作的简便性。

Kras-(LSL-G12D)-2.png

图4.  荷瘤小鼠体内肿瘤细胞体积随时间增长的变化。


KPC胰腺癌模型

小鼠是目前成功建立的一种胰腺导管腺癌模型小鼠,具有很多与人胰腺癌相似的特点,如胰腺内皮细胞瘤形成,强烈的免疫反应。80%的KPC小鼠出现了肝转移和肺转移的现象。KPC小鼠包含了KRAS和TP53基因突变,而在人胰腺癌的研究中发现,分别有80%和70%的患者表达这两种突变蛋白。

KPC小鼠的P53基因含有一个显性抑制性点突变( TP53R172H ),KRAS基因含有一个条件性活化点突变(KRASG12D)。KRAS突变基因的上游含有lox-stop-lox终止序列,其在没有cre重组酶的条件下是不表达的。将Cre重组酶连接到PDX1的启动子后,其将在胰腺的腺泡、胰岛和导管中表达。在Cre介导的基因重组中,突变的KRAS基因含有的lox-stop-lox终止序列被切除,从而可在胰腺中表达KRASG12D蛋白。

验证数据-KPC小鼠模型-图1.png

图1 KPC小鼠模型的自发式性胰腺癌体,体积较大,表面不平整,多个结节状突起。

验证数据-KPC小鼠模型-图2.png

图2 KPC小鼠的胰腺癌体的HE染色结果。

胰腺细胞排列无序,组织结构呈不规则细胞团,可见胰腺导管增生,炎症细胞浸润,间质纤维形成,符合肿瘤组织结构特征。

验证数据-KPC小鼠模型-图3.png

图3 荷瘤小鼠胰腺肿瘤体积的变化。

野生型小鼠接种了KPC小鼠的胰腺癌细胞,随着时间推移,胰腺肿瘤体积越来越大。


通过以下三个类型的小鼠模型,相互交配可以获得上文所述的KPC小鼠,这三类小鼠也可分别与其他感兴趣的模型小鼠交配以满足不同的研究需要。

Trp53-(R172H) NM-KI-18028

Kras-(LSL-G12D) NM-KI-190003

Pdx1-Cre-Tg


发表文献 11篇

1. ENPP1-Regulated Extracellular Purine Metabolism Drives Pancreatitis-Mediated Pancreatic Cancer
发表年份:2026 来源杂志:GASTROENTEROLOGY

2. Fusobacterium nucleatum promotes tumor progression in KRAS p.G12D-mutant colorectal cancer by binding to DHX15
发表年份:2024 来源杂志:Nature Communications

3. Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis
发表年份:2024 来源杂志:Nature Communications

4. Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma
发表年份:2024 来源杂志:CANCER RESEARCH

5. Oncogenic KRAS induces arginine auxotrophy and confers a therapeutic vulnerability to SLC7A1 inhibition in non-small cell lung cancer
发表年份:2024 来源杂志:CANCER RESEARCH

6. The RNA binding protein RALY suppresses p53 activity and promotes lung tumorigenesis
发表年份:2023-04-25 来源杂志:Cell Reports

7. Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy
发表年份:2023 来源杂志:Nature Communications

8. Chromatin Remodeling Induced by ARID1A Loss in Lung Cancer Promotes Glycolysis and Confers JQ1 Vulnerability
发表年份:2022 来源杂志:CANCER RESEARCH

9. Gene Coexpression Network Characterizing Microenvironmental Heterogeneity and Intercellular Communication in Pancreatic Ductal Adenocarcinoma: Implications of Prognostic Significance and Therapeutic Target
发表年份:2022 来源杂志:Frontiers in Oncology

10. KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma
发表年份:2020 来源杂志:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

11. The deubiquitylase OTUD3 stabilizes GRP78 and promotes lung tumorigenesis
发表年份:2019 来源杂志:Nature Communications

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