The aim of this study is to use transgenic mice as models to understand the role of the human Familial Mediterranean Fever (FMF) gene, MEFV, in the pathogenesis of the disease. FMF is an inherited disease with periodic fever and abdominal pain. It is very frequent in the Middle East and can be fatal due to amyloidosis and renal failure if untreated. We have cloned this gene through linkage study and positional cloning, and found that patients with FMF have point mutations in this gene. The gene is expressed specifically in maturing granulocytes, one of the target tissues of the disease process for FMF. MEFV encodes for a protein of unknown function. We have generated transgenic mice with a deletion of the MEFV gene to understand the normal function of this gene. Mice with homozygous MEFV deletions grew normally and have not shown any visible defects nor suffered any specific diseases. However, detailed analysis of granulocytes indicated that the control of apoptosis, a process through which unwanted cells can be recycled, is defective in these animals. We are also generating transgenic mice with point mutations in the MEFV gene, mimicking those found in FMF patients. Such mice can be used to confirm the importance of the mutations for the induction of the disease, and to study the pathophysiology of the disease, which may lead to a better treatment of FMF patients.
