Development and characterization of a pig model of TET2-mediated clonal hematopoiesis

As people age, stem cells can develop mutations that lead to the formation of clones of white blood cells. This process is known as clonal haematopoiesis. The mutated blood cells are a risk factor for cardiovascular disease. Patients with clonal haematopoiesis also have poorer survival after surgery. The underlying mechanisms are not well understood. Experimental evidence to date has come mainly from small animal models, which often do not adequately reflect disease mechanisms and effects in humans. We therefore plan to develop pigs with a stem cell mutation that leads to clonal haematopoiesis. Such a large animal model should allow us to characterise the importance and mechanisms of clonal haematopoiesis in cardiovascular disease and to investigate new treatment options.