23 May 2008
GM mouse research in jeopardy
Decades of research in comparative genomics are based on the assumption that specific comparable genes in rodents are identical to the equivalent genes in humans; but new research shows that a gene’s phenotype is heavily species dependent.
Researchers from the University of Michigan selected 120 genes that are essential to human survival and reproduction and studied previous data from knockouts of the equivalent “identical” genes in mice [1]. If the 120 genes performed the same functions in humans and mice, the knockout mice would have died, or at least been unable to reproduce. But 22% of the essential genes in humans weren’t essential in mice and had no such effect. This throws serious doubt on the basis for using genetically modified (GM) mice to research human disease.
The Dr Hadwen Trust has long been concerned that equivalent genes in humans and mice don’t have the same phenotypic effects. Last year we had a special funding call to find projects that replace GM mice in research.
One very promising research project that arose from this is being conducted by researchers at the University of York. This project involves creating targeted gene disruptions in adult mesenchymal stem cells extracted from donated human bone marrow. These cells have the ability to differentiate into different types of cells in vitro including bone, cartilage and muscle cells.
The researchers then knock out specific genes in the mesenchymal stem cells before differentiating them and growing them into 3D structures of the selected cell types. This novel technique avoids the problems with species differences seen in knockout mouse experiments, and has potential to replace some GM mouse research. Read more about our project here
Reference
1. Liao BY, Zhang J (2008). Null mutations in human and mouse orthologs frequently result in different phenotypes. Proceedings of the National Academy of Sciences 105:6987-6992.