Knockout of DNase1l1l abrogates lens denucleation process and causes cataract in zebrafish.
Biochim Biophys Acta Mol Basis Dis
; 1866(5): 165724, 2020 05 01.
Article
en En
| MEDLINE
| ID: mdl-32061775
ABSTRACT
Removal of nuclei in lens fiber cells is required for organelle-free zone (OFZ) formation during lens development. Defect in degradation of nuclear DNA leads to cataract formation. DNase2ß degrades nuclear DNA of lens fiber cells during lens differentiation in mouse. Hsf4 is the principal heat shock transcription factor in lens and facilitates the lens differentiation. Knockout of Hsf4 in mouse and zebrafish resulted in lens developmental defect that was characterized by retaining of nuclei in lens fiber cells. In previous in vitro studies, we found that Hsf4 promoted DNase2ß expression in human and mouse lens epithelial cells. In this study, it was found that, instead of DNase2ß, DNase1l1l is uniquely expressed in zebrafish lens and was absent in Hsf4-/- zebrafish lens. Using CRISPR-Cas9 technology, a DNase1l1l knockout zebrafish line was constructed, which developed cataract. Deletion of DNase1l1l totally abrogated lens primary and secondary fiber cell denucleation process, whereas had little effect on the clearance of other organelles. The transcriptional regulation of DNase1l1l was dramatically impaired in Hsf4-/- zebrafish lens. Rescue of DNase1l1l mRNA into Hsf4-/- zebrafish embryos alleviated its defect in lens fiber cell denucleation. Our results in vivo demonstrated that DNase1l1l is the primary DNase responsible for nuclear DNA degradation in lens fiber cells, and Hsf4 can transcriptionally activate DNase1l1l expression in zebrafish.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Catarata
/
Regulación del Desarrollo de la Expresión Génica
/
Proteínas de Pez Cebra
/
Desoxirribonucleasas
/
Factores de Transcripción del Choque Térmico
/
Cristalino
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2020
Tipo del documento:
Article
País de afiliación:
China