title: Isolation, genomic organization, and expression analysis of the mouse and rat homologs of MEFV, the gene for familial mediterranean fever.
abstract: 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 regulate 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 sequence of 2304 bp, while the rat homolog has nine exons with a coding sequence of 2253 bp. A considerable amino acid sequence homology was observed between 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 predicted rodent proteins have several important domains and signals found in human pyrin, including a B-box zinc finger domain, Robbins-Dingwall nuclear localization signal, and coiled-coil domain. However, perhaps because of an ancient frame-shift mutation, neither the mouse nor the rat protein has an intact C-terminal B30.2 domain, in which most FMF-associated mutations have been found in human MEFV. Nevertheless, like the human gene, mouse Mefv is expressed in peripheral blood granulocytes but not lymphocytes. Consistent with its expression in granulocytes, Mefv was detected at high levels in the primary follicles and marginal zones of the splenic white pulp. Mefv is localized on mouse Chromosome (Chr) 16, region A3-B1, extending a region of synteny with human Chr 16p13.3. Development of knockout and knockin mouse models may provide further insights into the functional evolution of this gene.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N-214, Bethesda, Maryland 20892-1820, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Chae
authors.forename: M
authors.initials: M
authors.lastname: Centola
authors.forename: I
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: A
authors.initials: A
authors.lastname: Dutra
authors.forename: M
authors.initials: M
authors.lastname: Tran
authors.forename: G
authors.initials: G
authors.lastname: Wood
authors.forename: K
authors.initials: K
authors.lastname: Nagaraju
authors.forename: D W
authors.initials: DW
authors.lastname: Kingma
authors.forename: P P
authors.initials: PP
authors.lastname: Liu
authors.forename: D L
authors.initials: DL
authors.lastname: Kastner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005796:Genes / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C000604192:MEFV protein, human; C000604193:Mefv protein, mouse; D011506:Proteins; D000071198:Pyrin; D012333:RNA, Messenger; D004247:DNA