Scientists Revolutionize the Creation of Genetically Altered Mice to Model Human Disease
Image: Courtesy of Cell Press
Whitehead Institute Founding Member Rudolf Jaenisch, who helped transform the study of genetics by creating the first transgenic mouse in 1974, is again revolutionizing how genetically altered animal models are created and perhaps even redefining what species may serve as models.
“This new method is a game changer,” says Jaenisch, who is also a professor of biology at MIT. “We can now make a mouse with five mutations in just three to four weeks, whereas the conventional way would take three to four years. And it’s rather straightforward, probably even easier than the conventional way.”
Scientists create models in mice by altering specific genes that have been associated with a given disease. The models allow for the study of the development and course of the disease and the effects of various interventions, including genetic and chemical. For the past 20 years, the creation of such models has remained relatively unchanged: scientists insert a piece of DNA into a mouse embryonic stem (ES) cell, inject the modified cell into a very early-stage embryo, called a blastocyst, then implant this developing ball of cells into a foster female mouse. The whole process can take years and tens of thousands of dollars to establish a mouse strain with, for example, a single copy of a gene “knocked out”. Such knockouts can only be created in very few species, including mice and rats, whose ES cells can be grown and modified reliably.
The new approach used by scientists in Jaenisch’s lab bypasses ES cells to quickly and efficiently produce mice with mutations in both copies of multiple genes. In next week’s issue of the journal Cell, Haoyi Wang, Hui Yang, and Chikdu Shivalila describe their technique, which is based on a system that certain bacteria use to fend off viral attacks.