Generation of Fbn1 conditional null mice implicates the extracellular microfibrils in osteoprogenitor recruitment

Jason R. Cook, Silvia Smaldone, Carmine Cozzolino, Maria del Solar, Sui Lee-Arteaga, Harikiran Nistala, Francesco Ramirez

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 (Fbn1fneo) that contains loxP sites bordering exon1 of Fbn1 and an frt-flanked neo expression cassette downstream of it. Fbn1fneo/+ mice were crossed with FLPeR mice and the resulting Fbn1Lox/+ progeny were crossed with Fbn1+/-;CMV-Cre mice to generate Fbn1CMV-/- mice, which were found to phenocopy the vascular abnormalities of Fbn1-/- mice. Furthermore, mating Fbn1Lox/+ mice with Prx1-Cre or Osx-Cre mice revealed an unappreciated role of fibrillin-1 microfibrils in restricting osteoprogenitor cell recruitment. Fbn1Lox/+ 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.

Original languageEnglish (US)
Pages (from-to)635-641
Number of pages7
JournalGenesis
Volume50
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Conditional gene inactivation
  • Fibrillin-1
  • Marfan syndrome
  • Osteogenesis

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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