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 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.
Liu
J P
JP
Department of Genetics and Development, Columbia University, New York, New York 10032.
Baker
J
J
Perkins
A S
AS
Robertson
E J
EJ
Efstratiadis
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004392:Dwarfism / Q000235:genetics*; D004622:Embryo, Mammalian; D006720:Homozygote; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D017354:Point Mutation; D011487:Protein Conformation; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology
D017931:DNA Primers; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1