MICE CARRYING NULL MUTATIONS OF THE GENES ENCODING INSULIN-LIKE GROWTH FACTOR-I (IGF-1) AND TYPE-1 IGF RECEPTOR (IGF1R)

Newborn mice homozygous for a targeted disruption of insulin-like grow th factor gene 1 (Igf-1) exhibit a growth deficiency similar in severi ty to that previously observed in viable Igf-2 null mutants (60% of no rmal birthweight). Depending on genetic background, some of the Igf-1( -/-) dwarfs die shortly after birth, while others survive and reach ad ulthood. In contrast, null mutants for the Igf1r gene die invariably a t birth of respiratory failure and exhibit a more severe growth defici ency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays i n ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf- 2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phen otypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revea led from the phenotypic differences between these mutants, are discuss ed.