Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)

TLDR

IGFs are essential for mouse embryonic development, as illustrated by distinct phenotypic differences among Igf-1, Igf-2, and Igf1r null mutants. Igf-1 null mice exhibit severe growth restriction (≈60 % of normal birthweight) with variable survival, whereas Igf1r null mice die at birth with more pronounced growth failure (≈45 % of normal size) and widespread organ hypoplasia; double mutants involving Igf1r show similar phenotypes, while combinations of Igf-1 or Igf-2 with Igf1r further exacerbate dwarfism to about 30 % of normal size.

Abstract

Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in 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 phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.