A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.
A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.
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由腺癌注射和体内生物发光成像介导的未分化多态性肉瘤的TRP53FL/FlptenFL/FL小鼠模型。
DOI：
10.1371/journal.pone.0183469
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Henry MD
中科院分区：
文献类型：
--
作者：
Buchakjian MR;Merritt NM;Moose DL;Dupuy AJ;Tanas MR;Henry MD
软组织肉瘤的小鼠遗传模型提供了对疾病病理生理学的关键见解，而疾病病理生理学往往无法从人类肿瘤样本或异种移植模型中提取。在本研究中，我们描述了腺病毒-Cre重组酶注射到Trp53fl/fl/Ptenfl/f1lox-Stop-lox荧光素酶小鼠体内的软组织肉瘤模型。两个实验组皮下或肌肉注射表达Cre重组酶的腺病毒后，病毒感染和基因重组在注射后24小时内100%外显。通过实时生物发光成像测量的荧光素酶表达随着时间的推移而增加，最初在病毒注射后强劲增加，随后随着原发肿瘤的发展和生长在接下来的几周内稳步上升。与皮下注射相比，肌肉注射更常与全身病毒分布的证据有关。所有小鼠在初次注射部位都出现了软组织肉瘤，根据肉瘤标志物的显微镜形态和免疫组织化学表达，组织学检查发现93%的肿瘤为侵袭性多形性肉瘤。在该免疫活性模型中，肉瘤中有淋巴细胞浸润，71%的肿瘤表达PD-L1。这是首次报道病毒-Cre介导的TrP53/Pten小鼠未分化多形性肉瘤模型。生物发光成像的特点，以及模型的高外显率和免疫学特性，使其适合于软组织肉瘤的临床前研究。
Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.
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影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
8.4
作者：
Edinger, M;Cao, YA;Contag, CH
通讯作者：
Contag, CH
影响因子：
6
作者：
Guijarro, Maria V.;Dahiya, Sonika;Hernando, Eva
通讯作者：
Hernando, Eva
影响因子：
3.3
作者：
Kawaguchi, K;Oda, Y;Tsuneyoshi, M
通讯作者：
Tsuneyoshi, M
影响因子：
3.7
作者：
Mito, Jeffrey K.;Riedel, Richard F.;Kirsch, David G.
通讯作者：
Kirsch, David G.