Hoeflich Andreas, Bünger Lutz, Nedbal Sabine, Renne Ulla, Elmlinger Martin W, Blum Werner F, Bruley Charlotte, Kolb Helmut J, Wolf Eckhard
Lehrstuhl für Molekulare Tierzucht und Biotechnologie/Genzentrum, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
Gen Comp Endocrinol. 2004 Apr;136(2):248-59. doi: 10.1016/j.ygcen.2003.12.019.
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.
转基因和基因敲除模型已成功用于确定不同生长因子的特定功能。然而，当生长受到影响时，尚不清楚不同的胰岛素样生长因子（IGF）组分中哪些实际上发生了改变。此外，也不清楚在生长升高或降低的情况下，是否存在IGF组分表达的独特或冗余模式。为了解决这些问题，我们使用了一组通过对高、低体重进行差异选择而产生的独特小鼠模型。这组小鼠模型由在不同实验室建立的8个品系组成。我们研究了这些小鼠品系中与生长相关基因的全身和局部表达，这些品系在体重和胴体重量以及鼻臀长度方面差异很大。作为一种严格保守的模式，与各自的低生长品系相比，所有高生长品系的血清IGF-I水平都显著升高。相比之下，血清IGF结合蛋白（IGFBP）浓度在响应生长选择时并未显示出明确的表达模式：某些高生长品系中IGFBP-3升高，高生长或低生长品系中IGFBP-2升高，高生长和低生长品系中IGFBP-4相似。IGFBP-2是部分低生长品系中唯一升高的IGFBP，这一事实表明，在所有其他IGFBP中，IGFBP-2是循环中生长的唯一但非必需的负效应因子。在以胴体重量特定增加为特征的选择育种组的肌肉组织中，我们发现了基因表达的冗余模式，这表明在肌肉组织生长选择过程中不存在组织特异性或唯一固定的表达模式。血清而非组织IGF-I水平在生长选择期间与生长严格正相关，这一发现表明内分泌IGF-I对小鼠出生后生长具有重要作用。
