The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, 
and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase 
complex acts as a tumor suppressor in several tissues and targets multiple 
transcriptional activators and protooncogenes for ubiquitin-mediated 
degradation. To understand Fbxw7 function in the murine intestine, in this 
study, we specifically deleted Fbxw7 in the murine gut using Villin-Cre 
(Fbxw7(ΔG)). In wild-type mice, loss of Fbxw7 in the gut altered homeostasis of 
the intestinal epithelium, resulted in elevated Notch and c-Jun expression, and 
induced development of adenomas at 9-10 mo of age. In the context of APC 
(adenomatous polyposis coli) deficiency (Apc(Min/+) mice), loss of Fbxw7 
accelerated intestinal tumorigenesis and death and promoted accumulation of 
β-catenin in adenomas at late but not early time points. At early time points, 
Fbxw7 mutant tumors showed accumulation of the DEK protooncogene. DEK expression 
promoted cell division and altered splicing of tropomyosin (TPM) RNA, which may 
also influence cell proliferation. DEK accumulation and altered TPM RNA splicing 
were also detected in FBXW7 mutant human colorectal tumor tissues. Given their 
reduced lifespan and increased incidence of intestinal tumors, 
Apc(Min/+)Fbxw7(ΔG) mice may be used for testing carcinogenicity and drug 
screening.