Genetic disruption of IGF binding proteins

Much recent work has begun to elucidate the individual contributions of IGF system legends and receptors to growth as well as specific differentiative events (1-3). In contrast, the required function(s) of IGFBPs, revealed by genetic approaches, continues to be relatively unexplored. The modest phenotype exhibited by IGFBP-2 null mice (4) is consistent with the possibility that compensation by other of the six "traditional" IGFBPs may mask required functions of the entire family. Moreover, additional proteins with IGF binding capacity have been recently identified (5) and potentially may complicate even further the analysis of individual IGFBP mutants. We here review our recent work that has lead to genetic disruption of two additional binding proteins, IGFBP-4 and IGFBP-6, and report initial results from analysis of homozygous mutant mice carrying these mutations.