By inference, the recovery of inserts affecting other genes in the IGF-II signalling pathway suggests that mutations in multiple genes may affect the same phenotype by acting on a common pathway. The insert in Igf2r was found to decrease the expression of the gene as assayed by northern blot analysis (data not shown). As IGF-II targets the igf2r to lysosomal degradation, mutations in the genes encoding either the receptor (Igf2r) or its ligand (Igf2) will affect the activity of the other, and result in a reduced endosomal trafficking of hydrolases necessary for reovirus disassembly [24]. Our **data** indicates there is a decrease in virus disassembly in 6B72 cells, consistent with a block at Anchorage-independent growth phenotypes of RIE-1 cell clones Figure 9 Anchorage-independent growth phenotypes of RIE-1 cell clones. 10 5 cells were suspended in media containing 1% agarose and plated in 6 well culture dishes. RIE-1 cells acquire the ability to grow in soft agar after being transfected with a vector expressing pro-IGF2 but not the IGF2 SV splice-variant (a). The vector inserted in the Ctcf gene (6B72) confers the ability to grow in soft agar, but the phenotype is suppressed by expression of IGF2 SV (b). Clones selected for reovirus resistance with gene trap vectors inserted into the Prss11, Igf2r and Anxa2 genes failed to grow in soft agar (c). RIE-1 cells expressing native IGF-II protein without the E-peptide grew in soft agar but the colonies were smaller (d) than produced by pro-IGF-2 (a), while the corresponding IGF-II A62T protein (E-peptide) did not transform RIE-1 cells to anchorage independence (d). Colonies were photographed (20×) after 7 days except (d) where the cells were photographed after 10 days.