Exon 1 was replaced with a modified exon 1 in which the codons corresponding to the residues 85 through 88 (the R-Smad binding site) and 266 through 267 (the Co-Smad binding site) were altered to code for alanines. A floxed neo cassette was inserted downsteam of the modified exon 1 and subsequently removed by germ line, cre mediated recombination. This allele is predicted to produce a protein product incapable of interacting with R-Smads and Smad4. (J:154718)