Abstract
Purpose:
Latent transforming growth factor beta binding protein 2 (ltbp2) is a member of the fibrillin/ltbp superfamily. In humans, mutations in LTBP2 are known to underlie autosomal recessive Weill-Marchesani syndrome, a condition characterized by ectopia lentis and microspherophakia.
Methods:
To better understand the role of ltbp2 in eye development, its expression in the developing mouse eye was visualized by in situ hybridization and immunofluorescence. Ltbp2-null mice were generated by homologous recombination and their ocular phenotype assessed by confocal microscopy.
Results:
In situ hybridization and immunofluorescence analysis suggested that, in mice, ltbp2 was not expressed until the end of the first postnatal week, when transcripts were first observed in the non-pigmented ciliary epithelium (NPCE). Microfibrils containing ltbp2 were detected on the surface of the NPCE and subsequently incorporated into the developing ciliary zonule. In ltbp2-null mice the ciliary zonule appeared to form normally but disintegrated at later time points leading to ectopia lentis. Lenses from ltbp2-null mice were transparent but slightly smaller than those from age-matched littermates.
Conclusions:
Ltbp2 is a component of the postnatal ciliary zonule where it appears to contribute to long-term zonule stability. Lens growth defects and progressive lens detachment in ltbp2-null mice are reminiscent of the ocular phenotype of patients with autosomal recessive Weill-Marchesani syndrome. Ltbp2-/- mice may thus represent a useful model to study the ocular complications associated with this condition.