OBJECTIVE: To investigate the expression of the familial Mediterranean fever 
(FMF) gene (MEFV) in human synovial fibroblasts.
METHODS: MEFV messenger RNA in synovial fibroblasts, chondrocytes, and 
peripheral blood leukocytes (PBLs) was analyzed by semiquantitative and 
real-time polymerase chain reaction and ribonuclease protection assay. The 
subcellular localization of pyrin, the MEFV product, was determined in 
transfected synovial fibroblasts and HeLa cells with plasmids encoding pyrin 
isoforms. Native pyrin was detected with an antipyrin antibody.
RESULTS: MEFV was expressed in synovial fibroblasts, but not in chondrocytes. 
Four alternatively spliced transcripts were identified: an extension of exon 8 
(exon 8ext) resulting in a frameshift that predicts a truncated protein lacking 
exons 9 and 10, the addition of an exon (exon 4a) predicting a truncated protein 
at exon 5, the in-frame substitution of exon 2a for exon 2, and the previously 
described removal of exon 2 (exon 2Delta). Exon 8ext transcripts represented 27% 
of the total message population in synovial fibroblasts. All other alternatively 
spliced transcripts were rare. Consensus and alternatively spliced transcripts 
were induced by lipopolysaccharide in synovial fibroblasts and PBLs. In 
transfected cells, the proteins encoded by all highly expressed splice forms 
were cytoplasmic. In contrast, native pyrin was predominantly nuclear in 
synovial fibroblasts, neutrophils, and dendritic cells, but was cytoplasmic in 
monocytes.
CONCLUSION: Several MEFV transcripts are expressed and inducible in synovial 
fibroblasts. A prominent isoform lacks the C-terminal domain that contains the 
majority of mutations found in patients with FMF. While recombinant forms of all 
major pyrin isoforms are cytoplasmic, native pyrin is nuclear in several cell 
types. Thus, mechanisms in addition to splicing patterns must control pyrin's 
subcellular distribution.