IGF-I is required for normal embryonic growth in mice.
IGF-I is a pleiotropic hormone reported to affect linear growth, glucose metabolism, organ homeostasis, and the immune and neurologic systems. In contrast to IGF-II, IGF-I is expressed at low levels embryonically and has been thought to be more important for postnatal growth and development. To investigate the role of IGF-I in normal development we generated mice with an inactive IGF-I gene by homologous recombination in ES cells. Heterozygous mice are healthy and fertile, but they are 10-20% smaller than wild-type littermates and have lower than normal levels of IGF-I. The size reduction is attributable to a decrease in organs and muscle and bone mass. However, all tissues appear histologically normal. At birth homozygous mutant mice (IGF-I-/-) are < 60% body weight of wild type. Greater than 95% of IGF-I-/- pups die perinatally. Histopathology is characterized by underdevelopment of muscle tissue. Lungs of late embryonic and neonates also appeared less organized with ill-defined alveolae. IGF-I appears to be essential for correct embryonic development in mice.
Powell-Braxton
L
L
Department of Endocrine Research, Genentech, Inc., South San Francisco, California 94080-4990.
Hollingshead
P
P
Warburton
C
C
Dowd
M
M
Pitts-Meek
S
S
Dalton
D
D
Gillett
N
N
Stewart
T A
TA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice / Q000002:abnormalities / Q000196:embryology* / Q000235:genetics; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D011247:Pregnancy
D007334:Insulin-Like Growth Factor I