Knocking Down Snrnp200 Initiates Demorphogenesis of Rod Photoreceptors in Zebrafish

Abstract EN

Purpose.

The small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene is a fundamental component for precursor message RNA (pre-mRNA) splicing and has been implicated in the etiology of autosomal dominant retinitis pigmentosa (adRP).

This study aims to determine the consequences of knocking down Snrnp200 in zebrafish.

Methods.

Expression of the Snrnp200 transcript in zebrafish was determined via whole mount in situ hybridization.

Morpholino oligonucleotide (MO) aiming to knock down the expression of Snrnp200 was injected into zebrafish embryos, followed by analyses of aberrant splicing and expression of the U4/U6-U5 tri-small nuclear ribonucleoproteins (snRNPs) components and retina-specific transcripts.

Systemic changes and retinal phenotypes were further characterized by histological study and immunofluorescence staining.

Results.

Snrnp200 was ubiquitously expressed in zebrafish.

Knocking down Snrnp200 in zebrafish triggered aberrant splicing of the cbln1 gene, upregulation of other U4/U6-U5 tri-snRNP components, and downregulation of a panel of retina-specific transcripts.

Systemic defects were found correlated with knockdown of Snrnp200 in zebrafish.

Only demorphogenesis of rod photoreceptors was detected in the initial stage, mimicking the disease characteristics of RP.

Conclusions.

We conclude that knocking down Snrnp200 in zebrafish could alter regular splicing and expression of a panel of genes, which may eventually trigger rod defects.