A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.
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.
Siracusa
L D
LD
Department of Microbiology and Immunology, Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA. siracusa@lac.jci.tju.edu
McGrath
R
R
Ma
Q
Q
Moskow
J J
JJ
Manne
J
J
Christner
P J
PJ
Buchberg
A M
AM
Jimenez
S A
SA
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
D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse