| Summary: | <p>Abstract</p> <p>Background</p> <p>Rybp (Ring1 and YY1 binding protein) is a zinc finger protein which interacts with the members of the mammalian polycomb complexes. Previously we have shown that Rybp is critical for early embryogenesis and that haploinsufficiency of <it>Rybp </it>in a subset of embryos causes failure of neural tube closure. Here we investigated the requirement for <it>Rybp </it>in ocular development using four <it>in vivo </it>mouse models which resulted in either the ablation or overexpression of <it>Rybp</it>.</p> <p>Results</p> <p>Our results demonstrate that loss of a single <it>Rybp </it>allele in conventional knockout mice often resulted in retinal coloboma, an incomplete closure of the optic fissure, characterized by perturbed localization of <it>Pax6 </it>but not of <it>Pax2</it>. In addition, about one half of <it>Rybp-/- <-> Rybp+/+ </it>chimeric embryos also developed retinal colobomas and malformed lenses. Tissue-specific transgenic overexpression of <it>Rybp </it>in the lens resulted in abnormal fiber cell differentiation and severe lens opacification with increased levels of <it>AP-2α </it>and <it>Sox2</it>, and reduced levels of <it>βA4-crystallin </it>gene expression. Ubiquitous transgenic overexpression of <it>Rybp </it>in the entire eye caused abnormal retinal folds, corneal neovascularization, and lens opacification. Additional changes included defects in anterior eye development.</p> <p>Conclusion</p> <p>These studies establish <it>Rybp </it>as a novel gene that has been associated with coloboma. Other genes linked to coloboma encode various classes of transcription factors such as <it>BCOR</it>, <it>CBP</it>, <it>Chx10</it>, <it>Pax2</it>, <it>Pax6</it>, <it>Six3</it>, <it>Ski</it>, <it>Vax1 </it>and <it>Vax2</it>. We propose that the multiple functions for <it>Rybp </it>in regulating mouse retinal and lens development are mediated by genetic, epigenetic and physical interactions between these genes and proteins.</p>
|
|---|
