Dnase2b-KO Mouse

Dnase2b, the ancestral gene of the DNase2 family, has been conserved in synteny with the Uox gene across 700 million years of animal evolution. It is an enzyme with a key function in nuclear degradation, especially in the mouse lens [1,2]. In the context of lens development, this function is crucial as the lens needs to undergo organelle and nuclear degradation to become transparent, suggesting its importance in maintaining tissue transparency and proper development [2,3].

In Celf1-targeted knockout mice, the RNA-binding protein Celf1 directly binds to the mRNA of Dnase2b to maintain its high levels. This event is necessary for Cdk1-mediated lamin A/C phosphorylation to initiate nuclear envelope breakdown and DNA degradation in fiber cells. Celf1 deficiency leads to ectopic up-regulation of p21Cip1 and down-regulation of Dnase2b, resulting in severe eye defects/cataract [2]. In Xenopus, inactivation of dnase2b by CRISPR/Cas9 produces lens defects similar to human cataracts, including nuclei retention in lens fiber cells and actin fibers disorganization [4].

In conclusion, Dnase2b plays an essential role in nuclear degradation, particularly in lens development. Findings from gene knockout models in mice and Xenopus have revealed its significance in preventing cataract-like phenotypes. These studies highlight the importance of Dnase2b in maintaining proper lens function and offer insights into the molecular mechanisms underlying cataract formation [2,4].

References:

1. Mori, Giulia, Delfino, Danila, Pibiri, Paola, Rivetti, Claudio, Percudani, Riccardo. 2022. Origin and significance of the human DNase repertoire. In Scientific reports, 12, 10364. doi:10.1038/s41598-022-14133-w. https://pubmed.ncbi.nlm.nih.gov/35725583/

2. Siddam, Archana D, Gautier-Courteille, Carole, Perez-Campos, Linette, Paillard, Luc, Lachke, Salil A. 2018. The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development. In PLoS genetics, 14, e1007278. doi:10.1371/journal.pgen.1007278. https://pubmed.ncbi.nlm.nih.gov/29565969/

3. Iida, Atsumi, Tabata, Yoko, Baba, Yukihiro, Fujii, Tomoaki, Watanabe, Sumiko. 2014. Critical roles of DNase1l3l in lens nuclear degeneration in zebrafish. In Biochimie, 106, 68-74. doi:10.1016/j.biochi.2014.07.025. https://pubmed.ncbi.nlm.nih.gov/25127661/

4. Viet, Justine, Reboutier, David, Hardy, Serge, Paillard, Luc, Gautier-Courteille, Carole. 2020. Modeling ocular lens disease in Xenopus. In Developmental dynamics : an official publication of the American Association of Anatomists, 249, 610-621. doi:10.1002/dvdy.147. https://pubmed.ncbi.nlm.nih.gov/31872467/