Modeling ocular lens disease in Xenopus
- 24 December 2019
- journal article
- research article
- Published by Wiley in Developmental Dynamics
- Vol. 249 (5), 610-621
- https://doi.org/10.1002/dvdy.147
Abstract
Background Ocular lens clouding is termed as cataract, which depending on the onset, is classified as congenital or age‐related. Developing new cataract treatments requires new models. Thus far, Xenopus embryos have not been evaluated as a system for studying cataract. Results We characterized the developmental process of lens formation in Xenopus laevis tailbuds and tadpoles, and we disrupted the orthologues of three mammalian cataract‐linked genes in F0 by CRISPR/Cas9. We assessed the consequences of gene inactivation by combining external examination with histochemical analyses and functional vision assays. Inactivating the key metazoan eye development transcription factor gene pax6 produces a strong eye phenotype including an absence of eye tissue. Inactivating the genes for gap‐junction protein and a nuclease, gja8 and dnase2b, produces lens defects that share several features of human cataracts, including impaired vision acuity, nuclei retention in lens fiber cells, and actin fibers disorganization. We tested the potential improvement of the visual acuity of gja8 crispant tadpoles upon treatment with the molecular chaperone 4‐phenylbutyrate. Conclusion Xenopus is a valuable model organism to understand the molecular pathology of congenital eye defects, including cataracts, and to screen molecules with a potential to prevent or reverse cataracts.Keywords
Funding Information
- Bouygues Telecom
- NIH Blueprint for Neuroscience Research (R01EY021505, R01EY029770)
This publication has 57 references indexed in Scilit:
- High efficiency TALENs enable F0 functional analysis by targeted gene disruption in Xenopus laevis embryosBiology Open, 2013
- Transcription factors involved in lens development from the preplacodal ectodermDevelopmental Biology, 2012
- iSyTE:IntegratedSystemsTool forEye Gene DiscoveryInvestigative Ophthalmology & Visual Science, 2012
- Lens fibre cell differentiation and organelle loss: many paths lead to clarityPhilosophical Transactions B, 2011
- Molecular and cellular aspects of amphibian lens regenerationProgress in Retinal and Eye Research, 2010
- Gene expression profiles of lens regeneration and development inXenopus laevisDevelopmental Dynamics, 2009
- Posterior capsule opacificationExperimental Eye Research, 2009
- The role of the lens actin cytoskeleton in fiber cell elongation and differentiationSeminars in Cell & Developmental Biology, 2006
- Nuclear cataract caused by a lack of DNA degradation in the mouse eye lensNature, 2003
- A Missense Mutation in the Human Connexin50 Gene (GJA8) Underlies Autosomal Dominant “Zonular Pulverulent” Cataract, on Chromosome 1qAmerican Journal of Human Genetics, 1998