Assessment of growth parameters and life span of GHR/BP gene-disrupted mice.
GH has many biological roles, including promotion of growth. Most, if not all, of its roles are achieved through interaction with its receptor. We chose to study the effects of loss of GH signaling on growth and aging in a mouse model for Laron Syndrome (LS) in which the GHR/BP gene has been disrupted. We observed that mice homozygous for the disruption (-/-) were significantly smaller than normal wild-type (+/+) mice as well as mice heterozygous for the disruption, even at 1.5 yr of age. IGF-I levels were also significantly lower in the -/- mice and remained low as the mice aged. IGFBP-3 levels were severely reduced in the -/- mice, whereas IGFBP-1, -2, and -4 levels remained unchanged. Finally, the -/- mice lived significantly longer than +/+ and +/- mice. The latter result contradicts the anti-aging GH data and suggests the need for further analysis of GH and aging.
Coschigano
K T
KT
Edison Biotechnology Institute, Ohio University, Athens 45701, USA.
Clemmons
D
D
Bellush
L L
LL
Kopchick
J J
JJ
D000375:Aging / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006720:Homozygote; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice / Q000235:genetics / Q000254:growth & development; D008807:Mice, Inbred BALB C; D011986:Receptors, Somatotropin / Q000235:genetics*; D015430:Weight Gain / Q000502:physiology
D002352:Carrier Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein