Chasing the BSE agent

The UK and its anxious neighbours are currently focusing on foot and mouth disease but agricultural researchers are still working on a much deeper and worrying problem: BSE and its human form, new variant CJD. Unlike foot and mouth disease, much remains unknown about the aberrant prion protein agent of BSE and how it causes disease. One of the biggest stumbling blocks to research is the lack of a relatively simple and reliable test to show early infection with the agent. But researchers now reporting in Nature Medicine (March 2001) provide the first hint that this mysterious disease may leave a molecular footprint during the early stages of infection that could provide a new means of testing for the disease. Michael Clinton and a colleague at the Roslin Institute near Edinburgh, Scotland and another colleague at the Institute for Animal Health in Edinburgh have looked in detail at the expression of messenger RNA molecules in cells from control, healthy mice and compared them with cells from mice infected by the BSE agent. The aim was to see if there might be any early indication of infection outside of the brain where classical signs of the late-stage disease are found. When they looked at spleen cells from the mice, although the level of many thousands of different transcripts in normal and infected mice were comparable, the team found that one transcript was found at a significantly lower in the spleen cells of infected mice. Study of the sequence of this transcript revealed that it was similar to one designated as erythroid differentiation-related factor (EDRF) named because of its previous isolation from mouse erythroblasts and human bone marrow. The team also found that different strains of transmissible spongiform encephalopathy (TSE) in both mice and hamsters led to a similar drop in the level of expression of the EDRF-encoding mRNA. The team then went on to look at samples of material taken from cattle known to be infected with BSE and sheep with scrapie. Compared with normal controls, expression of EDRF was considerably decreased in bone marrow of cattle displaying initial clinical signs of BSE and in the blood of sheep showing clinical signs of scrapie. The team do not yet know how the observed changes in EDRF activity relate to infection. The effect may be indirect rather than direct. Nor is it clear at this stage precisely how good a diagnostic marker …