Growth selection in mice reveals conserved and redundant expression patterns of the insulin-like growth factor system Andreas Hoeflich, a, * ,1 Lutz B€ unger, b,c,1 Sabine Nedbal, a Ulla Renne, d Martin W. Elmlinger, e Werner F. Blum, f Charlotte Bruley, b Helmut J. Kolb, g and Eckhard Wolf a a Lehrstuhl fu ¨ r Molekulare Tierzucht und Biotechnologie/Genzentrum, Ludwig-Maximilians-Universita ¨ t, 81377 Munich, Germany b Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK c Scottish Agricultural College, Animal Breeding and Genetics Department, Roslin EH26 0PH, UK d Forschungsinstitut fu ¨ r die Biologie landwirtschaftlicher Nutztiere, 18196 Dummerstorf, Germany e Sektion Endokrinologie, Universita ¨ ts-Kinderklinik, 72076 Tu ¨ bingen, Germany f Lilly Deutschland GmbH, 61350 Bad Homburg, Germany g Institut fu ¨ r Klinische Chemie, Sta ¨ dtisches Krankenhaus Mu ¨ nchen-Harlaching, 81545 Munich, Germany Received 20 November 2003; revised 22 December 2003; accepted 23 December 2003 Abstract Transgenic and knockout models have been used successfully in order to attribute specific functions to distinct growth factors. However, it is not clear which from the different IGF-components are actually altered when growth is affected. Furthermore it is not clear if unique or redundant patterns of IGF-component expression are present under conditions of elevated or reduced growth. To address these questions we have used a unique set of mouse models generated by divergent selection for high and low body growth. The set of mouse models consisted of eight mouse lines established in different laboratories. We have studied systemic and local expression of growth relevant genes in these mouse lines highly diverging for body and carcass weights but also for nose-rump lengths. As a strictly conserved pattern, serum IGF-I levels were dramatically increased in all H-lines if compared with the respective L-lines. By contrast serum IGFBP concentrations did not reveal clear patterns of expression in response to growth selection: IGFBP-3 was elevated in some H-lines, IGFBP-2 was increased in H- or L-lines and IGFBP-4 was similar in H- and L-lines. The fact that IGFBP-2 was the only IGFBP elevated in part of the L-lines, identifies IGFBP-2 as an exclusive although facultative negative effector for growth in the circulation among all other IGFBPs. In muscle tissue from selected breeding groups characterized by specific increases of the carcass weights we found redundant patterns of gene expression indicating the absence of tissue-specific or uniquely fixed expression patterns during growth selection within muscle tissue. The finding that serum but not tissue IGF-I levels were strictly positively correlated with growth during growth selection argues for an important role of endocrine IGF-I for postnatal growth in mice. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Growth selection; Body weight; Muscle; Gene expression; GH; IGF-I; IGFBPs 1. Introduction Control of growth is one of the most important fea- tures of life. To date, transgenic and knockout models as a gene-driven approach have been employed successfully in order to attribute specific functions to distinct growth factors (Efstratiadis, 1998). However, it is unclear, how a complex organism is dealing with the broad set of growth factors, e.g., if there are general patterns of growth control or if growth control is achieved by a unique combination of different expression levels of different growth factors. It is also not known, which of the identified growth factors are in fact regulated in a context of phenotypic selection for altered growth. These questions can ideally be answered by employment of mouse models generated via the phenotype-driven * Corresponding author. Fax: +49-89-2180-76849. E-mail address: hoeflich@lmb.uni-muenchen.de (A. Hoeflich). 1 A.H. and L.B. contributed equally to this project. 0016-6480/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ygcen.2003.12.019 www.elsevier.com/locate/ygcen General and Comparative Endocrinology 136 (2004) 248–259 GENERAL AND COMPARATIVE ENDOCRINOLOGY