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Generation of Fbn1 conditional null mice implicates the extracellular microfibrils in osteoprogenitor recruitment
Author(s) -
Cook Jason R.,
Smaldone Silvia,
Cozzolino Carmine,
del Solar Maria,
LeeArteaga Sui,
Nistala Harikiran,
Ramirez Francesco
Publication year - 2012
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.22022
Subject(s) - fibrillin , marfan syndrome , biology , microbiology and biotechnology , phenocopy , pathogenesis , ectopia lentis , null allele , extracellular , conditional gene knockout , mutant , genetics , extracellular matrix , immunology , gene , phenotype , medicine
Loss‐of‐function experiments in mice have yielded invaluable mechanistic insights into the pathogenesis of Marfan syndrome (MFS) and implicitly, into the multiple roles fibrillin‐1 microfibrils play in the developing and adult organism. Unfortunately, neonatal death from aortic complications of mice lacking fibrillin‐1 ( Fbn1 −/− mice) has limited the scope of these studies. Here, we report the creation of a conditional mutant allele ( Fbn1 fneo ) that contains loxP sites bordering exon1 of Fbn1 and an frt‐flanked neo expression cassette downstream of it. Fbn1 fneo /+ mice were crossed with FLPeR mice and the resulting Fbn1 Lox /+ progeny were crossed with Fbn1 +/− ; CMV‐Cre mice to generate Fbn1 CMV −/− mice, which were found to phenocopy the vascular abnormalities of Fbn1 −/− mice. Furthermore, mating Fbn1 Lox /+ mice with Prx1‐Cre or Osx‐Cre mice revealed an unappreciated role of fibrillin‐1 microfibrils in restricting osteoprogenitor cell recruitment. Fbn1 Lox /+ mice are, therefore, an informative genetic resource to further dissect MFS pathogenesis and the role of extracellular fibrillin‐1 assemblies in organ development and homeostasis. genesis 50:635–641, 2012. © 2012 Wiley Periodicals, Inc.