The Effects of Genetic Background of Mouse Models of Cancer: Friend or Foe?

Abstract

Over the past century, mice have been selectively bred to give rise to the strains used in biomedical research today. Mouse models of cancer allow researchers to control variables of diet, environment, and genetic heterogeneity to better dissect the role of these factors in cancer in humans. Because of the important role of genetic background in cancer, the strain of the mouse can introduce confounding results in studies of mouse models if not properly controlled. Conversely, genetic variation between strains can also provide important new insights into cancer mechanisms. Here, the sources of genetic heterogeneity in mouse models are reviewed, with an explanation of how heterogeneity modifies cancer phenotypes.

Figure 1:

(A) The distribution of Mus musculus subspecies and their contribution to modern day classical inbred strains. Classical inbred strains used in biomedical research were developed from European “fancy” mice that were descended from East Asian “fancy” mice. Classical inbred strains are mixtures of the domesticus, musculus, castaneus, and molossinus subspecies of Mus musculus. In addition, pure subspecies have been inbred to give rise to the “wild-derived” strains. WSB/EiJ is a M. m. domesticus strain originating in Maryland, USA. PWK/PhJ is a M. m. musculus strain originating near Prague, Czech Republic. CAST/EiJ is a M. m. castaneus strain originating in Thonburi, Thailand. (B) The design of the Collaborative Cross to maximize genetic diversity across a panel of recombinant inbred strains. Eight founder strains include 5 classical inbred strains and 3 wild-derived strains. By varying the position of each founder in the different breeding funnels, polymorphisms in the mitochondria (m) and the Y chromosome (Y) can be equally represented across the resulting lines.