SPECTRUM OF BMP5 MUTATIONS FROM GERMLINE MUTAGENESIS EXPERIMENTS IN MICE

Over 40 years of mutagenesis experiments using the mouse specific-locu s test have produced a large number of induced germline mutations at s even loci, among them the short ear locus. We have previously shown th at the short ear locus encodes bone morphogenetic protein 5 (BMP5), a member of a large family of secreted signaling molecules that play key roles in axis formation, tissue differentiation, mesenchymal epitheli al interactions, and skeletal development. Here we examine 24 chemical - and radiation-induced mutations at the short ear locus. Sequence cha nges in the Bmp5 open reading frame confirm the importance of cysteine residues in the function of TGF beta superfamily members. The spectru m of N-ethyl-N nitrosourea-induced mutations also provides new informa tion about the basepair, sequence context, and strand specificity of g ermline mutations in mammals.