Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation.

ABSTRACT: F-box and WD40 domain protein 7 (FBXW7) is a component of the SKP1-CUL1-F-box protein (SCF) complex that mediates the ubiquitination of diverse oncogenic target proteins. The exploration of FBXW7 mutations in human primary cancer has revealed three mutation hotspots at conserved arginine residues (Arg⁴⁶⁵, Arg⁴⁷⁹, and Arg⁵⁰⁵) in the WD40 domain, which are critical for substrate recognition. To study the function of human FBXW7 ^R465C , the most frequent mutation in human malignancies, we generated a novel conditional knockin mouse line of murine Fbxw7 ^R468C corresponding to human FBXW7 ^R465C . Systemic heterozygous knockin of the Fbxw7 ^R468C mutation resulted in perinatal lethality due to defects in lung development

SUBMITTER: Ikenoue T 

PROVIDER: S-EPMC5792591 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature