This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bienvenu, G. Articles by Babajko, S. Search for Related Content PubMed PubMed Citation Articles by Bienvenu, G. Articles by Babajko, S.

Insulin-Like Growth Factor Binding Protein-6 Transgenic Mice: Postnatal Growth, Brain Development, and Reproduction Abnormalities

Unité de Recherche (G.B., D.S., P.G., Y.L.B., S.B.), Institut National de la Santé et de la Recherche Médicale, Unité 515, Croissance, Différenciation et Processus Tumoraux, Hôpital Saint Antoine, 75571 Paris Cedex 12, France; Physiologie de la Reproduction et des Comportements (P.F., P.M.), Unité Mixte de Recherch 6073 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours, 37380 Nouzilly, France; and Service d’Anatomo-Pathologie (M.B.), Hôpital Sainte Anne, 75014 Paris, France

Address all correspondence and requests for reprints to: Sylvie Babajko, Institut National de la Santé et de la Recherche Médicale, Unité 515, Hôpital Saint Antoine, 184 rue du Faubourg St. Antoine, 75571 Paris Cedex 12, France. E-mail: U515{at}st-antoine.inserm.fr.

In biological fluids, IGFs bind to six distinct binding proteins (IGFBP-1 to -6). IGFBP-6 is of particular interest because it has been shown to inhibit proliferation in many cell types and to be synthesized in the central nervous system (CNS). It also has the strongest affinity for IGF-II among the IGFBPs. To study IGFBP-6 function in vivo, we established IGFBP-6 transgenic mice in which human IGFBP-6 (hIGFBP-6) cDNA is expressed under the control of the glial fibrillary acidic protein (GFAP) promoter. Northern and Western blot analysis revealed strong transgene expression in the CNS. With histological examination of the CNS, cerebellum size and weight proved to be reduced by about 25% and 35%, respectively, and there were smaller numbers of differentiated, GFAP-expressing astrocytes than in wild-type mice. Between birth and 1 month of age, transgenic mice had high levels of circulating hIGFBP-6 and reduced plasma IGF-I, and, as a result, body weight was significantly reduced. Reproductive physiology was also affected. Litter size was reduced by 27% when wild-type males were mated with 3-month-old transgenic females and by 66% when mated with 6-month-old transgenic females. Histological examination of ovaries of transgenic mice revealed a marked decrease in weight and in the number of corpora lutea, suggesting altered ovulation, and circulating LH levels were reduced by 50%. Our results indicate that this new model of transgenic mouse may prove to be a useful tool in elucidating the in vivo role of IGFBP-6 in the brain, especially in regard to hypothalamic control, and in reproductive physiology.

This article has been cited by other articles:

				X. Wang, L. Lu, Y. Li, M. Li, C. Chen, Q. Feng, C. Zhang, and C. Duan Molecular and functional characterization of two distinct IGF binding protein-6 genes in zebrafish Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1348 - R1357. [Abstract] [Full Text] [PDF]

				M. P. Sperandeo, P. Annunziata, A. Bozzato, P. Piccolo, L. Maiuri, M. D'Armiento, A. Ballabio, G. Corso, G. Andria, G. Borsani, et al. Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance Am J Physiol Cell Physiol, July 1, 2007; 293(1): C191 - C198. [Abstract] [Full Text] [PDF]

				S. B. Wheatcroft, M. T. Kearney, A. M. Shah, V. A. Ezzat, J. R. Miell, M. Modo, S. C.R. Williams, W. P. Cawthorn, G. Medina-Gomez, A. Vidal-Puig, et al. IGF-Binding Protein-2 Protects Against the Development of Obesity and Insulin Resistance Diabetes, February 1, 2007; 56(2): 285 - 294. [Abstract] [Full Text] [PDF]

				N. Ben Lagha, D. Seurin, Y. Le Bouc, M. Binoux, A. Berdal, P. Menuelle, and S. Babajko Insulin-Like Growth Factor Binding Protein (IGFBP-1) Involvement in Intrauterine Growth Retardation: Study on IGFBP-1 Overexpressing Transgenic Mice Endocrinology, October 1, 2006; 147(10): 4730 - 4737. [Abstract] [Full Text] [PDF]

				P. H. Larsen, A. G. DaSilva, K. Conant, and V. W. Yong Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice. J. Neurosci., February 22, 2006; 26(8): 2207 - 2214. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				V. Chandrashekar, D. Zaczek, and A. Bartke The Consequences of Altered Somatotropic System on Reproduction Biol Reprod, July 1, 2004; 71(1): 17 - 27. [Abstract] [Full Text] [PDF]