Isolation, genomic organization, and expression analysis of the mouse and rat homologs of MEFV, the gene for familial Mediterranean fever

Chae, JJ Centola, M Aksentijevich, I Dutra, A Tran, M Wood, G Nagaraju, K Kingma, DW Liu, PP Kastner, DL

Jj. Chae et al., Isolation, genomic organization, and expression analysis of the mouse and rat homologs of MEFV, the gene for familial Mediterranean fever, MAMM GENOME, 11(6), 2000, pp. 428-435

25

INGLESE

Article

Molecular Biology & Genetics

MAMMALIAN GENOME

0938-8990 → ACNP

11

6

2000

428 - 435

ISI

0938-8990(200006)11:6<428:IGOAEA>2.0.ZU;2-Z

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. Recently the FMF gene (MEFV ) was cloned; the protein product, pyrin/marenostrin, is thought to regulat e inflammation in myeloid cells. In this manuscript we report the mouse and rat homologs of MEFV. The murine gene contains ten exons with a coding seq uence of 2304 bp, while the rat homolog has nine exons with a coding sequen ce of 2253 bp. A considerable amino acid sequence homology was observed bet ween the mouse and human (47.6% identity and 65.5% similarity) and between the mouse and rat genes (73.5% identity and 82.1% similarity). The predicte d rodent proteins have several important domains and signals found in human pyrin, including a B-box zinc finger domain, Robbins-Dingwall nuclear loca lization signal, and coiled-coil domain. However, perhaps because of an anc ient frame-shift mutation, nei ther the mouse nor the rat protein has an in tact C-terminal B30.2 domain, in which most FMF-associated mutations have b een found in human MEFV. Nevertheless, like the human gene, mouse Mefv is e xpressed in peripheral blood granulocytes but not lymphocytes. Consistent w ith its expression in granulocytes. Mefv was detected at high levels in the primary follicles and marginal zones of the splenic white pulp, Mefv is lo calized on mouse Chromosome (Chr) 16, region A3-B1, extending a region of s ynteny with human Chr 16p13.3. Development of knockout and knockin mouse mo dels may provide further insights into the functional evolution of this gen e.