The role of the pRB/E2F pathway in erythropoiesis and cell cycle control

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Circulating blood contains two major types of cells. Red blood cells supply the oxygen required by all cells in our body to survive and white blood cells protect our body from invasion by foreign organisms. The balance in the number of these cells in our blood is a carefully regulated process which, when disturbed, can lead to a number of life-threatening blood diseases. Uncontrolled overgrowth of blood cells results in a particular type of cancer known as leukaemia. In contrast, when there is an insufficient number of red blood cells, not enough oxygen reaches cells from the brain and other vital organs and results in a condition known as anaemia. We have genetically engineered a mouse that lack the protein known as E2F4 and is unable to produce enough red blood cells and suffers from anaemia. This protein, E2F4, controls genes essential for the decision of cells to start or stop growing and multiplying. The E2F4-deficient mice therefore provide a new and powerful model to understand the mechanism by which disturbance of red blood cell numbers can lead to diseases such as leukaemia and other diseases of the blood. Identification of the genes controlled by E2F4 may provide new targets for the development of therapeutic drugs to combat these diseases.