Dysregulation of Spliceosomes Complex Induces Retinitis Pigmentosa-Like Characteristics in sf3b4-Depleted Zebrafish.
Am J Pathol
; 193(9): 1223-1233, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37263342
ABSTRACT
The SF3B4 gene encodes a highly conserved protein that plays a critical role in mRNA splicing. Mutations in this gene are known to cause Nager syndrome, a rare craniofacial disorder. Although SF3B4 expression is detected in the optic vesicle before it is detected in the limb and somite, the role of SF3B4 in the eye is not well understood. This study investigated the function of sf3b4 in the retina by performing transcriptome profiles, immunostaining, and behavioral analysis of sf3b4-/- mutant zebrafish. Results from this study suggest that dysregulation of the spliceosome complex affects not only craniofacial development but also retinogenesis. Zebrafish lacking functional sf3b4 displayed characteristics similar to retinitis pigmentosa (RP), marked by severe retinal pigment epithelium defects and rod degeneration. Pathway analysis revealed altered retinol metabolism and retinoic acid signaling in the sf3b4-/- mutants. Supplementation of retinoic acid rescued key cellular phenotypes observed in the sf3b4-/- mutants, offering potential therapeutic strategies for RP in the future. In conclusion, this study sheds light on the previously unknown role of SF3B4 in retinogenesis and provides insights into the underlying mechanisms of RP.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinose Pigmentar
/
Spliceossomos
Limite:
Animals
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2023
Tipo de documento:
Article