Department of Genetics, Stanford University, Stanford, California, United States of America.
PLoS One. 2010 Feb 24;5(2):e9402. doi: 10.1371/journal.pone.0009402.
Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.
新生儿喂养问题在多种遗传疾病中都有观察到，包括普拉德-威利综合征（PWS）。在生命后期，PWS 患者由于缺乏食欲控制而出现多食和肥胖。我们假设婴儿期生长不良和后期发生的多食是相关的，可能是由于下丘脑缺陷所致。在这项研究中，我们对新生野生型和 Snord116del 小鼠（一种 PWS 的小鼠模型，其簇状印迹 C/D 框 snoRNA 缺失）的下丘脑对母体剥夺的反应进行了基因表达微阵列分析。两种品系的新生儿饥饿反应与成年啮齿动物报道的反应明显不同。在 6 小时的母体剥夺后，受成年饥饿影响的基因在 5 天大的幼鼠下丘脑的表达没有变化。与成年啮齿动物不同，Nanos2 和 Pdk4 的表达水平增加，而 Pgpep1、Ndp、Brms1l、Mett10d 和 Snx1 的表达水平在新生儿剥夺后降低。此外，我们比较了新生后第 5 天和第 13 天的下丘脑基因表达谱，观察到显著的发育变化。值得注意的是，Snord116del 缺失小鼠和野生型同窝仔鼠的基因表达谱在所有时间点和条件下都非常相似，这表明 Snord116 在新生儿期的喂养调节中不起作用。
