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

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.