The lab mouse has long been essential to biomedical research. It has served as a standard model for human disease, often requiring changes to their genome to represent a specific disease or to understand the effects of new treatments.
However, mouse-based research relies on accurate genetic quality control of the model. A new research study spearheaded by geneticist and department chair Fernando Pardo-Manuel de Villena, PhD, and other collaborators at the UNC School of Medicine, recently examined hundreds of laboratory mouse models to test them for genetic accuracy.
Their findings, which were published in the journal Science, revealed that the genetic makeup of about half of the mouse models did not match expectations. This study highlights the importance of genetic quality control in research worldwide.
Fernando Pardo-Manuel de Villena, PhD
"We saw major inconsistencies and minor mismatches," said Pardo-Manuel de Villena, who is also an Oliver Smithies Investigator. "This is a big deal. When your research lacks rigor, you lose confidence in your results, it is not likely to be replicable, and you will waste resources, money, and animals."
Researchers found various pieces of foreign DNA encoding that are commonly used in many mouse models-such as fluorescence proteins and cre recombinase-that could greatly affect experimental outcomes and the validity of the findings, if the researchers do not know that they are there.
However, Pardo-Manuel de Villena is not without a plan. This past year, Carolina researchers developed a new strain GQC reporting system that verifies the genetic accuracy of their mouse models and shares the results with researchers across the United States and the world.
The new strain GQC reporting system was developed by the Mutant Mouse Resource and Research Centers (MMRRC) at UNC, which is part of a national network of archive and distribution facilities across the United States, including the University of North Carolina, University of California-Davis, the University of Missouri, and the Jackson Laboratory.
Examples of a MMRRC Strain GQC. Credit: MMRRC at UNC.
The collaborative effort has been funded by the National Institutes of Health (NIH) for more than twenty years and serves as a repository for laboratory mice that seeks to uphold the highest standards of experimental design and quality control.
"We act as an archive and a distribution center so that investigators from across the country can deposit and order mouse models for their research projects," said Jennifer Brennan, PhD, who is senior director of the Office of Research at the UNC School of Medicine and manager of the MMRRC at UNC. "Our new reporting system is a tool meant to start a conversation, not to cast blame, and we are here to help."
The MMRRC at UNC has created a series of short webinars to explain the features of the Strain GQC report.
