NIEHS/NTP Mouse Aging Study: Strain dependent differential cancer susceptibility

Authors

• J Dunnick
• R Herbert
• K Janardhan
• K Shockley
• A Pandiri
• A Merrick

Abstract

Genetic diversity is an important factor in age-related development of disease. The NIEHS/NTP has conducted a "mouse aging study" to examine genetic diversity as a variable for development of non-neoplastic and neoplastic diseases (lesions). Ten mouse strains* were selected for this study to represent ~ 90% of genetic diversity present in laboratory mice. A strain dependent susceptibility was noted in the neoplasms associated with liver, lung, uterus, ovary, mammary tissue, skeletal muscle, and lymphoid organs. At the end of two years, the neoplastic incidence for all tumors ranged from 10% - 87% in males, and 18% - 84% in females among the 10 mouse strains examined. The data from this study complements information in the Jackson Laboratory Mouse Phenome Database (http://www.phenome.jax.org/) and the Mouse Tumor Biology Database (http://tumor.informatics.jax.org/). Currently, environmental and drug safety assessments are conducted in a few animal strains with limited genetic diversity. This may be insufficient for evaluating the influence of individual genetic variability on chemical and drug toxicity, and for testing a range of toxicity responses that represent variations in the mammalian genome response to environmental hazards. This mouse aging study provides data to allow all stakeholders to better select mouse strains for toxicity studies based on background disease susceptibility, and to provide models to better characterize diseases associated with aging. This study could help in the identification of genetic variants that influence susceptibility or resistance to disease development. Pathology reviews for these studies are ongoing. *B6C3F1/J, C57BL/6J, A/J, C3H/HeJ, NOD.B1oSn-H2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ

Scientific Focus Area: Cancer Biology

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