Genetically diverse mice show human-like responses to heart attack

Modeling human diversity... in mice!

How can scientific research get answers when there's so much human diversity? Mice, of course!

If you survive a heart attack (myocardial infarction), you may be left with various kinds of damage to your heart, such as scarring or dilation, and that damage may be mild or severe. Complex genetic factors drive these outcomes, as well as the risk of developing cardiovascular disease in the first place.

Because humans are so genetically diverse, research using standard, inbred laboratory mice can’t replicate the wide range of patients’ post-attack heart damage. But mice from a genetically diverse panel, known as the Collaborative Cross, show a human-like variety of biological outcomes, a team at The Jackson Laboratory (JAX) and Monash University demonstrated in research published in Regenerative Medicine, a Nature partner journal.

Collaborative Cross mice, the brainchild of JAX scientists and their international collaborators, are the product of interbreeding eight genetically defined inbred mouse strains. Altogether, the resulting recombinant mouse strains reflect more genetic diversity than the entire human population.

 Genetically diverse mouse populations reveal secrets of the genomeDiscoveries in JAX-founded Collaborative Cross, Diversity Outbred populations show value of multi-parent model organism systemsmulti-parent-mouse-populations-reveal-genomic-secrets

 The Rosenthal LabInvestigating the role of growth factors, stem cells and the immune system in cardiovascular and skeletal muscle disease and regeneration.Nadia Rosenthal, professor and scientific director of mammalian genetics at JAX, and Ekaterina Salimova, a research fellow at the Australian Regenerative Medicine Institute at Monash University, and their colleagues documented large differences in survival, cardiac dilation and scar size among the eight founders and the Collaborative Cross strains. Gene expression profiling and quantitative locus mapping connected these differences to genetic variations in the mice.

“We found an exciting array of candidate genes and molecular pathways linked to adverse outcomes,” Rosenthal reports. “These could offer precision drug targets for treating the damage wrought by heart attacks in specific patients, dictated by their underlying genetic predispositions.”

Salimova et al.: Variable outcomes of human heart attack recapitulated in genetically diverse mice. npj Regenerative Medicine (2019)4:5;