Abnormal Chromosome Count May Protect Liver Cells from Injury

Abnormal Chromosome Count May Protect Liver Cells from Injury

The majority of liver cells contain an abnormal number of chromosomes, but these cells still retain their ability to divide. Researchers have long puzzled over why liver cells have unusual chromosome numbers, a state known as aneuploidy, and whether this genetic variation provides some benefit.

To test whether aneuploidy protect liver cells against liver injury, McGowan Institute for Regenerative Medicine faculty member Andrew Duncan, PhD, assistant professor in the University of Pittsburgh’s Department of Pathology, Division of Experimental Pathology, and colleagues at Oregon Health and Science University, Portland, Oregon, examined a mouse model of liver disease caused by deficiency of fumarylacetoacetate hydrolase (Fah). The researchers knew that if these mice acquire a second mutation in proteins that regulate Fah, these mutations provide a selective advantage and protect from liver damage.

To determine whether aneuploidy might contribute to these protective mutations, the Duncan team analyzed chromosomes from the mice. They found a striking prevalence in aneuploidy that lead to protective mutations in all mice that became completely resistant to liver injury.

The team’s results, presented in The Journal of Clinical Investigation, suggest that the selection of a specific aneuploid mutation can result in the adaptation of liver cells to chronic liver injury.