title: Ocular phenotype of Fbn2-null mice.
abstract: OBJECTIVE
  Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during development of the mouse eye. To test its role in morphogenesis, we examined the ocular phenotype of Fbn2(-/-) mice.
  
  
  METHODS
  Ocular morphology was assessed by confocal microscopy using antibodies against microfibril components.
  
  
  RESULTS
  Fbn2(-/-) mice had a high incidence of anterior segment dysgenesis. The iris was the most commonly affected tissue. Complete iridal coloboma was present in 37% of eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence of Fbn2 was partially compensated for by increased expression of fibrillin-1, although the resulting PM microfibrils were disorganized, compared with WTs. In colobomatous adult Fbn2(-/-) eyes, the PM failed to regress normally, especially beneath the notched region of the iris. Segments of the ciliary body were hypoplastic, and zonular fibers, although relatively plentiful, were unevenly distributed around the lens equator. In regions where the zonular fibers were particularly disturbed, the synchronous differentiation of the underlying lens fiber cells was affected.
  
  
  CONCLUSIONS
  Fbn2 has an indispensable role in ocular morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals implies a previously unsuspected role in optic fissure closure. The observation that fiber cell differentiation was disturbed in Fbn2(-/-) mice raises the possibility that the attachment of zonular fibers to the lens surface may help specify the equatorial margin of the lens epithelium.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Shi
authors.forename: Yidong
authors.initials: Y
authors.lastname: Tu
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.forename: Steven
authors.initials: S
authors.lastname: Bassnett
mesh_terms: D000818:Animals; D003103:Coloboma / Q000473:pathology*; D003285:Contractile Proteins / Q000172:deficiency / Q000502:physiology; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D007498:Iris / Q000002:abnormalities*; D051379:Mice; D008810:Mice, Inbred C57BL; D020894:Microfibrils / Q000473:pathology; D008840:Microfilament Proteins / Q000172:deficiency* / Q000502:physiology; D010641:Phenotype; D011681:Pupil Disorders / Q000209:etiology; D054392:Adipokines
chemical_list: D003285:Contractile Proteins; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C000605728:Fbn2 protein, mouse
keywords: ciliary epithelium; ciliary zonule; coloboma; fibrillin; lens; optic fissure; pupillary membrane; tunica vasculosa lentis