The mouse ascending: translating human genetic variation to function
Inbred mice have been only modestly successful in modelling widely divergent clinical outcomes in human disease, due to their limited genetic background. As host genetics plays a significant role in disease susceptibility, pathogenic infection and treatment success, preclinical models that reflect human genetic variation are crucial for predicting disease course and developing precision therapies. Interbred panels of mouse strains offer allelic diversity that mimics human genetic variation with the requisite statistical power and resolution for dissecting complex traits.
Examples include analysis of cardiac repair amongst diverse mouse populations, which has uncovered surprising variation in cell composition and transcriptomic profiles that mimics the broad spectrum of regenerative trajectories in human patients, highlighting the potential for more genetically precise, tissue-specific treatments of degenerative diseases. The same mouse panels display a correspondingly wide range of responses to SARS-CoV-2 infection, implicating as yet unknown genetic factors contributing the clinical spectrum of COVID-19 disease susceptibility, yielding greater insight into the genetic architecture underlying COVID-19 disease risk and progression. Mouse diversity resources combined with gene editing offer exciting prospects for creating a future of predictive biology for individualized disease prevention and treatment.
The recorded seminar can be viewed here (CRC members login needed).
