Dissociation of somatic growth, time of sexual maturity, and life expectancy by overexpression of an RGD-deficient IGFBP-2 variant in female transgenic mice.
Impaired growth is often associated with an extension of lifespan. However, the negative correlation between somatic growth and life expectancy is only true within, but not between, species. This can be observed because smaller species have, as a rule, a shorter lifespan than larger species. In insects and worms, reduced reproductive development and increased fat storage are associated with prolonged lifespan. However, in mammals the relationship between the dynamics of reproductive development, fat metabolism, growth rate, and lifespan are less clear. To address this point, female transgenic mice that were overexpressing similar levels of either intact (D-mice) or mutant insulin-like growth factor-binding protein-2 (IGFBP-2) lacking the Arg-Gly-Asp (RGD) motif (E- mice) were investigated. Both lines of transgenic mice exhibited a similar degree of growth impairment (-9% and -10%) in comparison with wild-type controls (C-mice). While in D-mice, sexual maturation was found to be delayed and life expectancy was significantly increased in comparison with C-mice, these parameters were unaltered in E-mice in spite of their reduced growth rate. These observations indicate that the RGD-domain has a major influence on the pleiotropic effects of IGFBP-2 and suggest that somatic growth and time of sexual maturity or somatic growth and life expectancy are less closely related than thought previously.
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Andreas
A
Hoeflich
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Anja
A
Reyer
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Daniela
D
Ohde
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Nancy
N
Schindler
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Julia
J
Brenmoehl
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Marion
M
Spitschak
Institute for Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Martina
M
Langhammer
Institute for Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.
Armin
A
Tuchscherer
Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), 18196, Dummerstorf, Germany.|Ligandis GbR, 18276, Gülzow-Prüzen, Germany.
Elisa
E
Wirthgen
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, 81377, Munich, Germany.
Ingrid
I
Renner-Müller
Institute of Veterinary Pathology, LMU Munich, 80539, Munich, Germany.
Rüdiger
R
Wanke
F. Hoffmann-La Roche Ltd., pRED, Pharma Research & Early Development, DTA Neuroscience, 4070, Basel, Switzerland.
Friedrich
F
Metzger
Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität, 80336, Munich, Germany.
Maximilian
M
Bielohuby
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, 81377, Munich, Germany.|German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
Eckhard
E
Wolf
D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D005260:Female; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D008017:Life Expectancy; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D018971:Insulin-Like Growth Factor Binding Protein 2
AKT; IGFBP-2; aging; cell signaling; growth; reproductive development