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Postnatally Elevated Levels of Insulin-Like Growth Factor (IGF)-II Fail to Rescue the Dwarfism of IGF-I-Deficient Mice except Kidney Weight

Authors :
Cecilia Camacho-Hübner
Reinhold G. Erben
Corinna Moerth
I Renner-Mueller
Eckhard Wolf
Martin W. Elmlinger
Andreas Hoeflich
Marlon R. Schneider
Andreas Blutke
Source :
Endocrinology. 148:441-451
Publication Year :
2007
Publisher :
The Endocrine Society, 2007.

Abstract

This study tested whether elevated levels of IGF-II in the postnatal period can rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I+/− IIwt] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate carboxykinase promoter IGF-II transgenic mice [I+/− IItg], and [I+/+ IIwt], [I+/+ IItg], [I−/− IIwt], and [I−/− IItg] offspring were investigated. IGF-II levels were 11- and 6-fold higher in male and female [I−/− IItg] vs. [I−/− IIwt] animals. Western ligand blot analysis revealed markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum from IGF-I-deficient mice. These binding proteins were partially restored by overexpression of IGF-II. Analysis of weight data from the early postnatal period until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have no effect on body weight gain. A detailed analysis of body proportions, bone parameters, and organ weights of 60-d-old mice also failed to show effects of IGF-II with one important exception: in Igf1 mutant and also Igf1 intact male mice, IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P < 0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in kidney weight were associated with reduced phosphorylation of p38 MAPK. In summary, our genetic model shows that substantial amounts of IGF-II in the circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice but increase absolute and relative kidney weights of normal and IGF-I-deficient male mice, suggesting a gender-specific role of IGF-II for kidney growth.

Details

ISSN :
19457170 and 00137227
Volume :
148
Database :
OpenAIRE
Journal :
Endocrinology
Accession number :
edsair.doi.dedup.....640f98dc92714298c3b5500ddb9fb13d
Full Text :
https://doi.org/10.1210/en.2006-0385