The Role of a PARP1 Genetic Variant in Development of Lupus
Location(s): United States
Many Americans have lupus and there is very little known about the etiology of the disease. Lupus has no cure. Our research suggests that people with a mutation in a specific DNA repair gene might be predisposed to SLE. We will characterize this genetic mutation in a mouse model and in cells to determine if it is linked to development of lupus. Our work is significant because it will provide biomarkers for SLE and also we will learn how mutations in DNA repair genes result in lupus. Our work may provide knowledge that can lead to more effective treatment for this disease.
The Specific Aims of the application are 1) To test the hypothesis that mice harboring the PARP1 GV develop lupus and 2) To test the hypothesis that the PARP1 SNP we have identified as being linked to SLE in humans results in compromised DNA repair. To achieve these aims we will generate mice harboring the PARP1 GV and characterize the development of lupus. We will also characterize this variant in tissue culture cells for its ability to participate in DNA rpair and characterize the lymphocytes of individuals with the PARP1 variant to determine if they have compromised DNA repair. This exploratory project will provide a rigorous test of our hypothesis and has the potential to provide mechanistic insights regarding the link between aberrant DNA repair and lupus.