Effects of FVB-NJ and C57Bl-6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient miceReport as inadecuate




Effects of FVB-NJ and C57Bl-6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice - Download this document for free, or read online. Document in PDF available to download.

Transgenic Research

, Volume 16, Issue 2, pp 193–201

First Online: 06 January 2007Received: 28 August 2006Accepted: 13 November 2006

Abstract

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.

KeywordsFVB-NJ C57Bl-6J Strain iNOS Breast Cancer Polyomavirus middle T antigen Mouse AbbreviationsiNOSinducible nitric oxide synthase

PyMTpolyomavirus middle T antigen

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Author: Sarah A. Davie - Jeannie E. Maglione - Cathyryne K. Manner - Dmitri Young - Robert D. Cardiff - Carol L. MacLeod - Lesl

Source: https://link.springer.com/







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