This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Organism Phenotypes
Defects in the human MSH2gene lead to HNPCC. Research has been conducted using model organisms lacking the MSH2 gene, or with mutant MSH2, in order to observe the mutant phenotypes that result. Studies have been conducted using RNA interference (RNAi) to knock out the homologous MSH2gene in each organism or target mutagenesis to create mutant MSH2 genes. Gene conservation between the human MSH2 gene and MSH2 homologs likely means that phenotypes seen in model organisms will be similar to phenotypes in humans. Several organism-specific databases such as MGI (mouse), WormBase (worm), FlyBase (fruit fly), and ZFIN (zebra fish) were used to identify the phenotypes caused by lack of or mutant MSH2.
Mutant phenotypes between mouse, worm, fruit fly, and zebra fish are very similar. The main phenotype that was observed in all organisms was an increase in spontaneous mutation rate. This phenotype fits well with the known role of MSH2 as a DNA mismatch repair protein. Furthermore, increase tumorigenesis was a common phenotype observed due to mutant MSH2. All mutant phenotypes for mouse, worm, fruit fly, and zebra fish can be seen at these links.
Analysis
Similar mutant phenotypes between model organisms suggests that the gene and protein functions of MSH2 are well conserved. Any of these model organisms could be used to study mutation rate of mutant MSH2. Mouse is the only one of these model organisms that can form tumors and thus should be used to study how mutant MSH2 affects tumorigenesis.