Characterizing Animal Models

Because the genomes of most experimental and some spontaneous animal models are sequenced, one type of information about cancer models that researchers want to evaluate is the genotype.  Genotype refers to the specific set of normal and variant regions of the genomic DNA in the cells. In organisms with pairs of chromosomes it is important to remember that variations can be observed on one or both members of a pair of chromosomes or genes, leading to situations of homozygosity (having the same version) or heterozygosity (having different versions). To perform genotyping, researchers employ a variety of techniques and computational approaches to link the regions of the genome that are associated with a particular cancer incidence, and to use this information to find the human genes that are associated with the same cancer.  This may include investigation of the genomic framework found in spontaneous and induced animal models.  It may also include the analysis of the genomic composition of primary and metastatic tumors, since these may differ from each other as well.

The compilation of information about the observable state of the biology, physiology, and disease manifestations in experimental and spontaneous cancer models is termed phenotyping. Phenotypes result from both the expression of the genes in an organism, as well as environmental factors that influence the organism. Interactions between genes and environmental influences affect organisms.  Phenotyping is considered by some to represent more of an organism-level observation, but can encompass the molecular-level differences in nucleotides, proteins, and chemical compounds as well.  Researchers most often develop the cancer- and tumor-related phenotype of a given strain through comparison to the phenotype of normal animals of the same strain.  The types of disease-related phenotypes that researchers catalog at the present time is increasingly broad as the techniques and equipment used in the clinic are developed and implemented to make them reliable tools for animal models as small as mice.

Linking genotype to phenotype is a challenging task, and the strategies will vary depending on the focus of the research.  Further, some phenotypes will be generated by features of cells that are unrelated to specific underlying DNA sequence alterations.  Epigenetics investigations are currently underway on many aspects of disease states that may offer insights on the instigation of cancerous states or on outcomes.

An excellent overview of many of the techniques and strategies to investigate human cancer offers insights into many of the methods that are also used on animal model systems. Some techniques and technologies for genotyping and phenotyping will be similar among animal models.  Others may vary by species.  For a deeper look at the strategies employed in different species and resources related to them, investigate the navigation options at the left.