Southern blot analysis of tail DNA from F1 offspring of both ApcCKON and ApcΔ580 lines confirmed the germline transmission of modified Apc allele (Figure 1B). Mice that are heterozygous for ApcΔ580 mutation are viable but have a significantly reduced lifespan (Figure 1C). These results suggested that deletion of exon 14 indeed results in either loss or abnormal function of the Apc gene product. ApcΔ580/+ mice have median survival of 5 mo of age (Figure 1C), with progressive signs of rectal bleeding and anemia. Similar to the results reported with an independently generated ApcΔ580/+ conditional mouse strain [14], ApcΔ580/+ mice had more than 100 (120 ± 37, n = 11) intestinal tumors at the time of their death (Figure S1). Inactivation of wild-type Apc is an important prerequisite for tumor development. We analyzed 30 intestinal tumors from ApcΔ580/+ mice by in vitro transcription and translation assay, but none of them showed truncated Apc products (unpublished data), indicating that the most likely mechanism of wild-type Apc inactivation is by allelic loss. The mutant allele had to be maintained and transmitted through male mice, as ApcΔ580/+ females were frequently not healthy enough to successfully nurse their own pups because of their tumor burden.