Mouse Genome Analysis Reveals New Disease Models

An international consortium working to create a catalog of gene function for the entire mouse genome has released its first set of results. According to the report, which was published June 26 in Nature Genetics, the analysis of 3328 mouse genes revealed models for 360 human diseases. The group is making its data freely available to biomedical researchers.

The International Mouse Phenotyping Consortium (IMPC) is a collaboration of research institutions around the world. Its goal, according to its website, is to “provide the first functional annotation of a mammalian genome.”

Participating IMPC institutions—currently 18—aim to identify the function of each of the 20,000+ mouse genes. The first set of results encompasses about 15% of the protein-encoding genes in the mouse genome.

The laboratory mouse is commonly used as a model for human disease because of its genetic and physiologic similarity to humans. Researchers test the function of individual genes by knocking out (inactivating) 1 gene at a time in embryonic mouse stem cells and observing changes in the physiology or behavior of the resulting knockout mice.

In many cases, knockout mice become research models for corresponding genetic disorders in humans. Most genomic research to date has focused on common inherited diseases. In comparison, rare diseases are not well studied. “Over half of diagnosed rare diseases still have no known associated genes,” say the authors of the report.

IMPC data yields new knowledge in 3 areas, they write: (1) finding new mouse models for human diseases with a known genetic basis, (2) discovering genes associated with human diseases for which a specific genetic basis has not been identified, and (3) identifying genes with a possible (previously unknown) association with disease.

Findings revealed in this first set of data include the following:

• New mouse models for Bernard-Soulier syndrome type C, Bardet-Biedl syndrome 5, and Gordon-Holmes syndrome
• A candidate gene for arrhythmogenic right ventricular dysplasia 3
• New evidence of the function of 1092 previously uncharacterized genes

“Although next-generation sequencing has revolutionized the identification of new disease genes, there is still a lack of understanding of how these genes actually cause disease,” said corresponding author Dr. Damian Smedley, of Queen Mary University of London, in a press release. “These 360 new disease models that we've identified in mice represent the first steps of a hugely important international project. We hope researchers will be able to use this knowledge to develop new therapies for patients, which is ultimately what we're all striving to achieve.”

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.