title: A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.
abstract: Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos.
authors.affiliation: Department of Microbiology and Immunology, Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA. siracusa@lac.jci.tju.edu
authors.forename: L D
authors.initials: LD
authors.lastname: Siracusa
authors.forename: R
authors.initials: R
authors.lastname: McGrath
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.forename: J J
authors.initials: JJ
authors.lastname: Moskow
authors.forename: J
authors.initials: J
authors.lastname: Manne
authors.forename: P J
authors.initials: PJ
authors.lastname: Christner
authors.forename: A M
authors.initials: AM
authors.lastname: Buchberg
authors.forename: S A
authors.initials: SA
authors.lastname: Jimenez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003240:Connective Tissue Diseases / Q000235:genetics; D018076:DNA, Complementary; D004195:Disease Models, Animal; D016521:Electrophoresis, Gel, Pulsed-Field; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D054392:Adipokines
chemical_list: D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse