Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth.
To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only approximately 17% of normal and, in absolute magnitude ( approximately 5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants.
Lupu
F
F
Department of Genetics and Development, Columbia University, New York, New York 10032, USA.
Terwilliger
J D
JD
Lee
K
K
Segre
G V
GV
Efstratiadis
A
A
D000818:Animals; D001483:Base Sequence; D001824:Body Constitution; D001846:Bone Development; D004702:Endocrine Glands / Q000502:physiology; D005786:Gene Expression Regulation; D006128:Growth / Q000235:genetics*; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009929:Organ Size; D012333:RNA, Messenger / Q000302:isolation & purification; D011986:Receptors, Somatotropin / Q000235:genetics*; D015398:Signal Transduction; D014018:Tissue Distribution
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone