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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1451-1455
Hematopoietic-specific expression of MEFV, the gene
mutated in familial Mediterranean fever, and subcellular
localization of its corresponding protein, pyrin
Nicola Tidow,
Xiaoguang Chen,
Carsten Müller,
Seiji Kawano,
Adrian F. Gombart,
Nathan Fischel-Ghodsian, and
H. Phillip Koeffler
From the Department of Medicine and Department of Pediatrics and
Medical Genetics, Cedars-Sinai Medical Center, UCLA School of Medicine,
Los Angeles, CA.
Familial Mediterranean fever (FMF) is a recessively inherited
disorder characterized by recurrent, self-limited attacks of fever and
serositis and by infiltration of affected tissues by large numbers of
neutrophils. A candidate gene for FMF was identified by positional
cloning and named "MEFV." The corresponding protein was
named "pyrin." To elucidate the currently unknown function of
pyrin, we characterized its tissue distribution, regulation of
expression during hematopoietic differentiation, and subcellular localization. Reverse transcription-polymerase chain reaction analysis,
followed by hybridization with an internal oligonucleotide, demonstrated expression of MEFV in different populations of
peripheral blood cells. Among hematopoietic cell lines, MEFV
was almost exclusively expressed in cells of the myeloid lineage.
Furthermore, MEFV messenger RNA was strongly expressed within
24 hours of dimethyl sulfoxide-induced granulocytic differentiation of
HL-60 cells. Analysis of complementary DNA from human solid
tumor-derived cell lines revealed expression of MEFV in
several cell lines derived from colon and prostate cancers. Expression
of MEFV fused to enhanced green fluorescent protein showed that
pyrin localized in distinct patches in the cytoplasm, forming a
perinuclear cap. Taken together, MEFV is predominantly
expressed in myeloid cells and upregulated during myeloid
differentiation, and the corresponding protein, pyrin, is expressed in
the cytoplasm.
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