Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice.
Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice.
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DOI：
10.1007/s11248-006-9056-9
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发表时间：
2007-04
影响因子：
3
通讯作者：
Ellies LG
中科院分区：
文献类型：
--
作者：
Davie SA;Maglione JE;Manner CK;Young D;Cardiff RD;MacLeod CL;Ellies LG
对小鼠进行基因操纵的能力使我们对不同基因产物在人类疾病中的作用的理解取得了快速进展。由于 FVB/NJ (FVB) 品系的高繁殖力，通常会产生转基因小鼠，而由于 129/SvJ 胚胎干细胞具有促进种系传递的能力，因此在 129/SvJ-C57Bl/6J 品系中开发出基因靶向小鼠。基因靶向小鼠通常与 C57Bl/6J (B6) 背景回交，以便与现有数据进行比较。基因修饰剂已被证明可以调节乳腺癌小鼠模型中的乳腺肿瘤潜伏期，众所周知，FVB 品系对乳腺肿瘤敏感，而 B6 品系则更具抵抗力。由于 B6 背景的基因靶向小鼠经常被培育成 FVB 品系的多瘤病毒中 T (PyMT) 乳腺癌小鼠模型，因此我们试图了解不同遗传背景对所得表型的影响。我们培育了缺乏诱导型一氧化氮合酶 (iNOS) 的小鼠，直到它们在 FVB 和 B6 品系的 PyMT 模型中是同源的。我们的结果表明，两个背景中平均肿瘤潜伏期的巨大差异（分别为 53 天和 92 天）影响了辨别 Nos2 基因突变引起的较小潜伏期差异的能力。此外，B6 菌株中较长的潜伏期能够对肿瘤形成进行更详细的分析，表明个体肿瘤的发育不是随机的，而是在 #1 腺体中启动并在早期和晚期阶段进行。 NO 的产生影响早期发生的肿瘤，表明 iNOS 诱导的 NO 与更具侵袭性的肿瘤表型相关，这与 iNOS 表达与乳腺癌进展呈正相关的人类临床数据一致。对肺转移的检查与这些发现一致，仅在 B6 背景下，与 PyMT/iNOS+/+ 小鼠相比，PyMT/iNOS−/− 小鼠的肺转移显着减少。我们的数据表明，B6 背景下的 PyMT 为研究炎症诱发的乳腺癌提供了一个有用的模型。
The ability to genetically manipulate mice has led to rapid progress in our understanding of the roles of different gene products in human disease. Transgenic mice have often been created in the FVB/NJ (FVB) strain due to its high fecundity, while gene-targeted mice have been developed in the 129/SvJ-C57Bl/6J strains due to the capacity of 129/SvJ embryonic stem cells to facilitate germline transmission. Gene-targeted mice are commonly backcrossed into the C57Bl/6J (B6) background for comparison with existing data. Genetic modifiers have been shown to modulate mammary tumor latency in mouse models of breast cancer and it is commonly known that the FVB strain is susceptible to mammary tumors while the B6 strain is more resistant. Since gene-targeted mice in the B6 background are frequently bred into the polyomavirus middle T (PyMT) mouse model of breast cancer in the FVB strain, we have sought to understand the impact of the different genetic backgrounds on the resulting phenotype. We bred mice deficient in the inducible nitric oxide synthase (iNOS) until they were congenic in the PyMT model in the FVB and B6 strains. Our results reveal that the large difference in mean tumor latencies in the two backgrounds of 53 and 92 days respectively affect the ability to discern smaller differences in latency due to the Nos2 genetic mutation. Furthermore, the longer latency in the B6 strain enables a more detailed analysis of tumor formation indicating that individual tumor development is not stoichastic, but is initiated in the #1 glands and proceeds in early and late phases. NO production affects tumors that develop early suggesting an association of iNOS-induced NO with a more aggressive tumor phenotype, consistent with human clinical data positively correlating iNOS expression with breast cancer progression. An examination of lung metastases, which are significantly reduced in PyMT/iNOS−/− mice compared with PyMT/iNOS+/+ mice only in the B6 background, is concordant with these findings. Our data suggest that PyMT in the B6 background provides a useful model for the study of inflammation-induced breast cancer.
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影响因子：
2.4
作者：
Eblaghie, MC;Song, SJ;Jung, HS
通讯作者：
Jung, HS
影响因子：
11.2
作者：
Qiu, TH;Chandramouli, GVR;Liu, ET
通讯作者：
Liu, ET
影响因子：
8.4
作者：
Loibl, S;Buck, A;Kauffmann, M
通讯作者：
Kauffmann, M
DOI：
10.1073/pnas.57.4.1068
发表时间：
1967-01-01
影响因子：
11.1
作者：
LAW, LW;TING, RC;LECKBAND, E
通讯作者：
LECKBAND, E
影响因子：
2.5
作者：
Le Voyer, T;Lu, ZC;Hunter, K
通讯作者：
Hunter, K