June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Characterization of early eye developmental defects in a new Rbm24 conditional knockout mouse model
Author Affiliations & Notes
  • Shaili Patel
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Soma Dash
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Salil Anil Lachke
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
    Center for Bioinformatics and Computational Biology, University of Delaware, Newark, Delaware, United States
  • Footnotes
    Commercial Relationships   Shaili Patel, None; Soma Dash, None; Salil Lachke, None
  • Footnotes
    Support  NIH/NEI R01 EY029770
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2066. doi:
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      Shaili Patel, Soma Dash, Salil Anil Lachke; Characterization of early eye developmental defects in a new Rbm24 conditional knockout mouse model. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2066.

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Abstract

Purpose : Early eye development involves regulatory interactions between the optic vesicle and the overlying surface ectoderm that are necessary for formation of the lens and the correct placement of the retina. While signaling and transcriptional regulation in early eye development is well characterized, the significance of RBPs and post-transcriptional gene expression control, is less clear. Germline deletion of the RNA-binding protein (RBP) gene, Rbm24, in mice (Rbm24-/-) perturbs these regulatory events, resulting in severe early eye defects such as microphthalmia (small eye) and anophthalmia (absence of eye). Rbm24 is expressed in both the optic vesicle and the presumptive lens ectoderm and how its activities in these tissues impacts eye development. Therefore, as a first step toward dissecting the tissue-specific role of Rbm24, Rbm24 compound conditional knockout mice were generated and characterized.

Methods : Rbm24cKO (Rbm24+/--Rax-CreERT2:Rbm24flox:flox; termed Rbm24cKO) mice were generated by crossing Rbm24flox/flox mice with the tamoxifen-inducible Rax-Cre line that supports Cre expression in optic vesicle. Phenotypic characterization of the ocular defects was performed by marker analysis using immunofluorescence and confocal microscopy.

Results : Rbm24cKO mice exhibit fully penetrant early eye defects exhibiting features of microphthalmia and anophthalmia, similar to that of Rbm24-/- mice. The lens tissue in Rbm24cKO mice appears abnormal from early stage at E10.5. Further, Rbm24cKO mouse exhibit abnormal expression of key ocular transcription factor-encoding genes such as Sox2, Pax6, and Lhx2 in early eye development.

Conclusions : This work reports the development of a new Rbm24 compound conditional knockout mouse line. Phenotypic characterization of these mice show that Rbm24 is required in the optic vesicle for early eye and lens development. Further, these findings define a new layer of regulatory mechanism in early eye development, that involving Rbm24 and its downstream targets the key ocular transcription factors Pax6, Sox2, and Lhx2. Because these transcription factors are linked to anophthalmia/microphthalmia, this work also uncovers a potential mechanism for the eye defects observed in Rbm24 deficient mice.

This is a 2021 ARVO Annual Meeting abstract.

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