Format

Send to

Choose Destination

See 1 citation found by title matching your search:

PLoS One. 2018 Jun 20;13(6):e0199573. doi: 10.1371/journal.pone.0199573. eCollection 2018.

A G542X cystic fibrosis mouse model for examining nonsense mutation directed therapies.

Author information

1
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
2
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, United States of America.
3
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States of America.

Abstract

Nonsense mutations are present in 10% of patients with CF, produce a premature termination codon in CFTR mRNA causing early termination of translation, and lead to lack of CFTR function. There are no currently available animal models which contain a nonsense mutation in the endogenous Cftr locus that can be utilized to test nonsense mutation therapies. In this study, we create a CF mouse model carrying the G542X nonsense mutation in Cftr using CRISPR/Cas9 gene editing. The G542X mouse model has reduced Cftr mRNA levels, demonstrates absence of CFTR function, and displays characteristic manifestations of CF mice such as reduced growth and intestinal obstruction. Importantly, CFTR restoration is observed in G542X intestinal organoids treated with G418, an aminoglycoside with translational readthrough capabilities. The G542X mouse model provides an invaluable resource for the identification of potential therapies of CF nonsense mutations as well as the assessment of in vivo effectiveness of these potential therapies targeting nonsense mutations.

PMID:
29924856
PMCID:
PMC6010256
DOI:
10.1371/journal.pone.0199573
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center