Source:http://linkedlifedata.com/resource/pubmed/id/11316754
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2001-4-24
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pubmed:abstractText |
To clarify the role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) in postnatal growth regulation, we crossed hemizygous CMV-IGFBP-2 transgenic mice with hemizygous PEPCK-bGH transgenic mice, which are characterized by serum GH levels in the range of 2 microgram/ml. Four genetic groups were obtained: animals carrying both transgenes (GB), the GH (G) or the IGFBP-2 transgene (B), and nontransgenic controls (C). Male offspring were analyzed for serum levels of IGF-I, for serum and tissue levels of IGFBP-2, and for body and organ growth. Serum IGF-I levels were 2- to 3-fold increased (P < 0.001) in the GH-overexpressing groups, with no difference between G and GB mice. Serum IGFBP-2 levels were 4- to 9-fold (P < 0.001) increased both in B and GB vs. C and G mice. Western immunoblot analysis did not reveal differences in tissue IGFBP-2 levels between B and GB mice. IGFBP-2 levels were highest in pancreas, followed by skeletal muscle, heart, kidney, brain, skin, and spleen. No elevation of IGFBP-2 was found in the liver. Body weight gain of G and GB mice was significantly increased vs. C and B mice, resulting in almost 2-fold increased body weights at the age of 15 weeks. However, there was a significant reduction in body weight of GB vs. G mice (17%; P < 0.001) and of B vs. C mice (13%; P < 0.05). This was primarily caused by a marked reduction of carcass weight (GB vs. G, 27%; B vs. C, 21%; P < 0.001). Measurements of nose-rump-length, organ (brain, heart, spleen, liver, pancreas, kidney), and tissue weights (skin, carcass, abdominal fat) in 5- and 15-week-old mice revealed several indications that the growth-inhibiting effect of IGFBP-2 overexpression was more marked in high-GH/IGF-I mice: 1) At 5 weeks of age, GB mice displayed a significant reduction of all growth parameters except for the weight of abdominal fat, when compared with G mice, whereas only brain weight was significantly reduced in B vs. C mice. 2) In 15-week-old animals, a significant reduction in all growth parameters, except for spleen and abdominal fat weights, was seen in GB vs. G mice, whereas only nose-rump-length and the weights of carcass and brain were significantly reduced in B vs. C mice. Our study demonstrates, for the first time, the potential of IGFBP-2 to inhibit GH-stimulated growth in giant transgenic mice, providing further evidence for an inhibitory effect of this IGFBP in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0013-7227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
142
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1889-98
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:11316754-Animals,
pubmed-meshheading:11316754-Female,
pubmed-meshheading:11316754-Growth,
pubmed-meshheading:11316754-Growth Hormone,
pubmed-meshheading:11316754-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:11316754-Insulin-Like Growth Factor I,
pubmed-meshheading:11316754-Liver,
pubmed-meshheading:11316754-Mice,
pubmed-meshheading:11316754-Mice, Transgenic,
pubmed-meshheading:11316754-Organ Size,
pubmed-meshheading:11316754-Weight Gain
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pubmed:year |
2001
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pubmed:articleTitle |
Growth inhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-binding protein-2.
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pubmed:affiliation |
Institutes of Molecular Animal Breeding, Animal Physiology, and Veterinary Pathology, Ludwig-Maximilian University, 81377 Munich, Germany.
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pubmed:publicationType |
Journal Article
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