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Fibrillins 1 and 2 perform partially overlapping functions during aortic development.

Fibrillin-rich microfibrils are extracellular assemblies that impart structural properties to the connective tissue. To elucidate the contribution of fibrillin-rich microfibrils to organogenesis, we have examined the vascular phenotype of a newly created strain of mice that completely lacks fibrillin-1 and the consequences of combined deficiency of fibrillins 1 and 2 on tissue formation. The results demonstrated that fibrillins 1 and 2 perform partially overlapping functions during aortic development. Fbn1-/- mice died soon after birth from ruptured aortic aneurysm, impaired pulmonary function, and/or diaphragmatic collapse. Analysis of the neonatal Fbn1-/- aorta documented a disorganized and poorly developed medial layer but normal levels of elastin cross-links. Transcriptional profiling revealed that aneurysm progression in Fbn1 null mice is accompanied by unproductive up-regulation of gene products normally involved in tissue repair and vascular integrity, such as plasminogen activator inhibitor-1, activin A, and cysteine-rich angiogenic protein 61. In contrast to Fbn1-/- mice, Fbn2 null mice had a well developed and morphologically normal aortic wall. However, virtually all Fbn1-/-;Fbn2-/- embryos and about half of the Fbn1+/-;Fbn2-/- embryos died in utero and displayed a significantly more severe vascular phenotype than Fbn1-/- mice. Consistent with a specialized function of fibrillin-2, electron microscopy visualized ultrastructurally different microfibrils in Fbn1 null compared with control cell cultures. Collectively, these data demonstrate that involvement of fibrillin-2 in the initial assembly of the aortic matrix overlaps in part with fibrillin-1 and that continued fibrillin-1 deposition is absolutely required for the maturation and function of the vessel during neonatal life.

Pubmed ID: 16407178


  • Carta L
  • Pereira L
  • Arteaga-Solis E
  • Lee-Arteaga SY
  • Lenart B
  • Starcher B
  • Merkel CA
  • Sukoyan M
  • Kerkis A
  • Hazeki N
  • Keene DR
  • Sakai LY
  • Ramirez F


The Journal of biological chemistry

Publication Data

March 24, 2006

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR049698
  • Agency: NIAMS NIH HHS, Id: AR42044
  • Agency: NIAMS NIH HHS, Id: AR48111
  • Agency: NIGMS NIH HHS, Id: F31 GM018511
  • Agency: NIGMS NIH HHS, Id: F31 GM018511-04
  • Agency: NIAMS NIH HHS, Id: R01 AR042044
  • Agency: NIAMS NIH HHS, Id: R01 AR042044-13

Mesh Terms

  • Activins
  • Alleles
  • Animals
  • Aorta
  • Cells, Cultured
  • Contractile Proteins
  • Cross-Linking Reagents
  • Crosses, Genetic
  • Cysteine-Rich Protein 61
  • Desmosine
  • Elastin
  • Fibroblasts
  • Genotype
  • Heterozygote
  • Immediate-Early Proteins
  • Immunoblotting
  • Inhibin-beta Subunits
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Microfibrils
  • Microfilament Proteins
  • Microscopy, Electron
  • Models, Genetic
  • Phenotype
  • Plasminogen Activator Inhibitor 1
  • RNA