The progression of P16 increases in mice as they age visible from the younger mice (left) to the older mice (right).
Researchers at University of North Carolina have engineered laboratory mice which exhibit a firefly gene that could help scientists study cancer development. The p16INK4a (p16) gene is known to play a role in tumor suppression, so the team introduced the firefly gene so that it would be activated whenever the p16 gene is.
Over time the mice with induced tumors were tracked and the glow was used to follow the activity of the p16 gene as it reacted to tumor progression. Some findings were that older mice glowed brighter, as expected, and the sites where cancer seemed to originate were particularly luminescent.
The researchers used these mice to make several unexpected discoveries. First, the group was able to track the accumulation of senescent cells in aging mice by assessing how brightly each mouse glowed. Surprisingly, the brightest animals were no more likely to die from spontaneous cancer than dimmer animals of the same age. That is, the number of senescent cells in the mouse did not predict its risk of dying.
Another surprise came from the disparities in p16 levels among the mice. The authors studied a large group of genetically identical animals that were all housed in the same way and fed the same diet. However, despite identical genetic and environmental conditions, the brightness of individual mice at any given age was highly variable, suggesting that factors beyond genetics and diet influence aging.
The glowing mice also provide a window into the formation of cancers. Expression of p16 is activated in the earliest stages of cancer formation to suppress cancer. Usually activation of p16 prevents cancer, but rarely this tumor suppressor mechanism fails and tumors develop, while still activating the p16 gene. As such, all tumors forming in these mice strongly glowed, allowing researchers to monitor early tumor formation in a wide variety of cancer types. In contrast to expectations, the researchers also found that p16 was activated not only in the tumor cells themselves, but also in normal, neighboring cells.
Press release: UNC researchers use luminescent mice to track cancer and aging in real-time
Study abstract: Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model