The Importance of Animal Models for Experimentation

Almost all of today's medical knowledge has been gleaned from animal experimentation, especially via model organisms.  The APC gene is a highly evolutionarily conserved protein, i.e. over the past hundreds of thousands of years, the APC gene has not changed very much among animal taxa.  Mice are likely the most common model organisms to be used for APC research--recall the picture that demonstrated adnomatous polyp formation from my earlier post "Adenomatous Polyp Formation."  In fact, lines of mutant mice are available for a wide variety of gene losses and APC knockout mice are no exception.  "Knockout" simply refers to a genetically engineered organism whose gene of interest has been inactivated.  By studying what happens in the absence of a particular protein, scientists are often able to discern that protein's role by comparing what occurs in a healthy organism versus a knockout organism.  Sure, humans aren't mice, but believe it or not, our DNA isn't too terribly different--our proteins are so similar that most of them can be identified as homologs, or evolutionary relatives across species!  Mice are relatively easy to maintain in a laboratory, the mouse genome has been sequenced, and much is known about mouse genetics.  These three reasons make mice great candidates for APC gene study.

Below, I've compiled a phylogenetic tree of the APC gene across a few different species.

From Top to Bottom: Bos taurus (domestic cow), Homo sapiens (human), Pan troglodytes (chimpanzee), Mus musculus (mouse), Rattus norvegicus (rat), Gallus gallus (chicken), Xenopus laevis (African clawed frog), Danio rerio (zebrafish), Drosophila melanogaster (fruit fly), and Canis lupus familiaris (domestic dog).  Courtesy of Protein Information Resource.  ClustalW Multiple Sequence Analysis.

While the chimpanzee has the closest homolog to the human APC gene, chimpanzees are not ideal model organisms for genetic engineering because they are large, expensive to maintain, and have a long life cycle.  This same reasoning applies to cows.  However, the next closest related homologs belong to the mouse and rat, making them the most ideal animal models for APC gene study in terms of gene relatedness.