Temporal changes of gene expression in mouse heart, kidney and lung during juvenile growth

Temporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size. To compare gene expression between fast-growing animals and more slowly growing animals, we extracted total mRNA from kidney and lung in 1-wk, 4-wk, and 8-wk-old mice (5 animals each).小鼠心脏、肾脏与肺脏中1周龄至4周龄再到8周龄的基因表达时序变化。哺乳动物出生后早期躯体生长极为迅速，但随后逐渐放缓，最终在多个组织中完全停止。我们提出假说：存在一套在多种组织中保守的出生后基因表达程序，该程序正是导致这种协同性生长减速的原因。本研究的基因芯片分析结果与该假说一致：在幼年小鼠的肾脏、肺脏与心脏中，共有超过1600个基因的表达随年龄呈现协同性变化，其中包含大量调控细胞增殖的基因。作为示例，我们重点关注了Igf2、Mest与Peg3这三个促生长基因，它们的表达均随年龄显著下调。综上，我们认为在出生后生命过程中存在一套大规模的基因表达调控程序。该程序涉及的诸多基因在多个器官中呈现协同表达调控，其中亦包含大量调控细胞增殖的基因。其中至少部分基因本身的表达显然受生长过程调控，这表明：在胚胎阶段，机体已建立一套支持多组织快速躯体生长的基因表达模式；但在出生后，这种生长会引发基因表达的负反馈调控变化，进而减缓并最终终止躯体生长，从而为成年个体的体型设定了根本性限制。为比较快速生长与慢速生长个体间的基因表达差异，我们从1周龄、4周龄及8周龄小鼠的肾脏与肺脏中提取了总mRNA（每组各5只小鼠）。