Transgenic approach for the study of physiological roles of pancreatic polypeptide

背景与目的：胰多肽是由胰岛和胰腺外分泌的F细胞分泌的一种含36个氨基酸的激素。PP在哺乳动物生理学中的确切功能仍有待确定。本研究旨在通过PP转基因小鼠的发育来研究PP的慢性过表达或缺失对小鼠的影响。方法：在巨细胞病毒即时早期增强子-鸡b-肌动蛋白杂合启动子(pCAGGS表达载体)的控制下，用小鼠PP基因构建PP转基因小鼠。结果：建立了一个独特的转基因小鼠品系，该品系在胰岛过度表达PP，而在包括脑在内的其他组织中低水平表达。血浆PP浓度是对照仔猪的20多倍。与对照组相比，PP转基因小鼠体重增加较少，食物摄入量和脂肪质量特别减少，这一结果在雄性小鼠中比在雌性小鼠中更明显。转基因小鼠的固体食物胃排空率降低，但氧耗和空腹瘦素水平正常。抗PP抗血清免疫中和可逆转转基因动物的表型变化。结论：PP可能部分通过调节胃排空参与摄食和体重调节。

Background & Aims : Pancreatic polypeptide (PP)is a 36-amino acid hormone produced by F cells within the pancreatic islets and the exocrine pancreas. The definitive function of PP in mammalian physiology still remains to be determined. This study was designed to examine the effects of chronic overexpression or deletion of PP through the development of PP transgenic mice. Methods : PP transgenic mice were created by using mouse PP cDNA under the control of the cytomegalovirus immediate early enhancer-chicken b-actin hybrid promoter (pCAGGS expression vector). Results : A unique line of transgenic mice were created that overexpress PP in the pancreatic islet with low levels of expression in other tissues including the brain. Plasma PP concentrations were more than 20 times higher than those of control littermates. PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared to controls, results which were more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization with anti-PP antiserum reversed the phenotypic changes of transgenic animals. Conclusions : These results indicate that PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying.