Genetic ablation of IGFBP-2 suggests functional redundancy in the IGFBP family

Abstract

Gene targeting allows mutations to be introduced selectively into any mouse locus of interest. This approach has already been used to demonstrate that insulin-like growth factor (IGF) peptides and receptors are required in vivo for normal prenatal growth. One of the IGFBP genes, IGFBP-2, has also been disrupted using gene targeting, and homozygous null BP-2 mice are characterized by a decreased spleen size most apparent during early postnatal stages and increased adult circulating levels of several other IGFBPs. These alterations are considered less dramatic than the phenotypes initially predicted based on the fetal IGFBP-2 expression pattern, although several physiological paradigms can be envisioned that will provide additional tests for specific aspects of IGFBP function. Since all six IGFBP genes are expressed during prenatal rodent development, as well as in adult tissues, the IGFBP-2 null phenotype must also be compared with genetic ablations involving members of other gene families and in the context of the other IGFBP expression patterns in rodent embryonic, extraembryonic, and uterine tissues.