The NIH Common Fund Knockout Mouse Phenotyping Program (KOMP2 is leading the way as part of the International Mouse Phenotyping Consortium (IMPC) (link is external) in understanding the aging process and diseases that occur later in life. The researchers are part of an ambitious project to genetically silence – or “knockout” – and characterize all genes that code for proteins in the mouse. This effort to generate "knockout mice" for every protein-coding gene is the first step before systematically carrying out a range of tests to understand each gene’s biological function, or “phenotype.” As part of the new effort within KOMP2 to understand aging, some knockout mice that appear normal as an adolescent or young adult mice are studied over longer period, to understand disease across the lifespan. The hope is to use mice to provide more insight into human diseases that occur later in life and the human aging process.
The KOMP2 program has made significant advances in understanding genes with previously unknown function in hearing, vision, and metabolism. However, these findings are primarily from mice at adolescent to young adult life stages. Since most human diseases appear later in life, learning more about gene function at later stages is needed to reveal new phenotypes and disease relationships. To do this, the same phenotyping methods used on young mice are then repeated when the mice are older. A “middle-aged adult” mouse is between 16 and 48 weeks of age, and a “late adult” is more than 48 weeks of age (see timeframe here). The testing for the late adult starts when the mice are about a year old (52 weeks). All data for knockout mice collected at these stages so far are now on the program’s data portal. In the portal, it is possible to compare the phenotypes from the same knockout mice throughout different points of the life span. The hope is for researchers throughout the biomedical sciences to use the data to generate new hypotheses about gene function later in life, and how it can give rise to the late-appearing diseases.
