Deletion of Gpr128 results in weight loss and increased intestinal contraction frequency

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:mazhiqianggege
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
AIM:To generate a Gpr128 gene knockout mouse model and to investigate its phenotypes and the biological function of the Gpr128 gene.METHODS:Bacterial artificial chromosome-retrieval methods were used for constructing the targeting vector.Using homologous recombination and microinjection technology,a Gpr128 knockout mouse model on a mixed 129/BL6 background was generated.The mice were genotyped by polymerase chain reaction(PCR)analysis of tail DNA and fed a standard laboratory chow diet.Animals of both sexes were used,and the phenotypes were assessed by histological,biochemical,molecular and physiological analyses.Semi-quantitative reverse transcription-PCR and Northern blotting were used to determine the tissue distribution of Gpr128mRNA.Beginning at the age of 4 wk,body weights were recorded every 4 wk.Food,feces,blood and organ samples were collected to analyze food consumption,fecal quantity,organ weight and constituents of the blood and plasma.A Trendelenburg preparation was utilized to examine intestinal motility in wild-type(WT)and Gpr128-/-mice at the age of 8 and 32 wk.RESULTS:Gpr128 mRNA was highly and exclusively detected in the intestinal tissues.Targeted deletion of Gpr128 in adult mice resulted in reduced body weight gain,and mutant mice exhibited an increased frequency of peristaltic contraction and slow wave potential of the small intestine.The Gpr128+/+mice gained more weight on average than the Gpr128-/-mice since 24 wk,being 30.81±2.84 g and 25.74±4.50 g,respectively(n=10,P<0.01).The frequency of small intestinal peristaltic contraction was increased in Gpr128-/-mice.At the age of 8 wk,the frequency of peristalsis with an intraluminal pressure of 3 cmH2O was 6.6±2.3 peristalsis/15 min in Gpr128-/-intestine(n=5)vs 2.6±1.7peristalsis/15 min in WT intestine(n=5,P<0.05).At the age of 32 wk,the frequency of peristaltic contraction with an intraluminal pressure of 2 and 3 cmH2O was 4.6±2.3 and 3.1±0.8 peristalsis/15 min in WT mice(n=8),whereas in Gpr128-/-mice(n=8)the frequency of contraction was 8.3±3.0 and 7.4±3.1peristalsis/15 min,respectively(2 cmH2O:P<0.05 vs WT;3 cmH2O:P<0.01 vs WT).The frequency of slow wave potential in Gpr128-/-intestine(35.8±4.3,36.4±4.2 and 37.1±4.8/min with an intraluminal pressure of 1,2 and 3 cmH2O,n=8)was also higher than in WT intestine(30.6±4.2,31.4±3.9 and 31.9±4.5/min,n=8,P<0.05).CONCLUSION:We have generated a mouse model with a targeted deletion of Gpr128 and found reduced body weight and increased intestinal contraction frequency in this animal model. AIM: To generate a Gpr128 gene knockout mouse model and to investigate its phenotypes and the biological function of the Gpr128 gene. METHODS: Bacterial artificial chromosome-retrieval methods were used for constructing the targeting vector. Using homologous recombination and microinjection technology, a Gpr128 knockout mouse model on a mixed 129 / BL6 background was generated. The mice were genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a standard laboratory chow diet. Animal of both sexes were used, and the phenotypes were assessed by histological, biochemical, molecular and physiological analyzes. Semi-quantitative reverse transcription-PCR and Northern blotting were used to determine the tissue distribution of Gpr128 mRNA. Endgin at the age of 4 wk, body weights were recorded every 4 weeks. Food, feces, blood and organ samples were collected to analyze food consumption, fecal quantity, organ weight and constituents of the blood and plasma. A Trendelenburg preparation was utiliz ed to examine intestinal motility in wild-type (WT) and Gpr128 - / - mice at the age of 8 and 32 wk.RESULTS: Gpr128 mRNA was highly and exclusively detected in the intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in reduced body weight gain, and mutant mice exhibited an increased frequency of peristaltic contraction and slow wave potential of the small intestine. The Gpr128 + / + mice were more weight on average than the Gpr128 - / - mice since 24 wk, being 30.81 ± 2.84 g and 25.74 ± 4.50 g, respectively (n = 10, P <0.01). The frequency of small intestinal peristaltic contraction was increased in Gpr128 - / - mice. At the age of 8 wk, the frequency of peristalsis with an intraluminal pressure of 3 cmH2O was 6.6 ± 2.3 peristalsis / 15 min in Gpr128 - / - intestine (n = 5) vs 2.6 ± 1.7 peristalsis / 15 min in WT intestine (n = 5, of peristaltic contraction with an intraluminal pressure of 2 and 3 cm H2O was 4.6 ± 2.3 and 3.1 ± 0.8 peristalsis / 15 min in WT mice (n = 8), while in G pr128-/ -mice (n = 8) the frequency of contraction was 8.3 ± 3.0 and 7.4 ± 3.1 peristalsis / 15 min, respectively (2 cmH2O: P <0.05 versus WT; 3 cmH2O: P < The wave potential in Gpr128 - / - intestine (35.8 ± 4.3, 36.4 ± 4.2 and 37.1 ± 4.8 / min with an intraluminal pressure of 1, 2 and 3 cmH2O, n = 8) was also higher than in WT intestine 31.4 ± 3.9 and 31.9 ± 4.5 / min, n = 8, P <0.05). CONCLUSION: We have generated a mouse model with a targeted deletion of Gpr128 and found reduced body weight and increased intestinal contraction frequency in this animal model.
其他文献
【摘 要】包装容器是包装设计中不可缺少的重要构成部分,是指包装的外观立体形态,是根据产品的实际需要,通过一定的材料、结构和技术手段创造出立体外观形态的活动过程。随着社会的发展,科技的进步,人们对包装容器造型设计的要求也越来越高,包装容器造型设计必须体现自身的实用功能与审美价值,还要遵循成本节约原则,为商品的保护、消费与审美功能服务,从而设计出最有特色的包装容器造型,达到促进销售的目的。  【关键词
同声传译是一个多元的传播结构.该文从信息传播的角度对此进行了操作,并寻求出一种教学模型,将翻译的本质描述为信息守恒,以期对全部翻译活动作出一种比较准确的、具体的、科学的
Erythropoietin (EPO) and granulocyte colonystimulating factor (G-CSF) are likely to play broad roles in the brain. We investigated the effects of combination th
今年以来,临猗县纪委就以深化“三转”为契机,以整合人力资源、聚焦主责主业为原则,超前一步,积极探索县级纪律检查体制改革。一是推进清理议事协调机构,精简瘦身。经过前后
Objective: The aim of our study was to measure and compare the serum hormone level of transplant group with blank control and castrated control groups after het
本文以四川建筑职业技术学院图书馆为例,介绍了以二级情报联系人为主导的适合高职院校自身发展学科馆员制度,并提出了改进措施。 Taking the library of Sichuan Constructi
本讲介绍了什么是文章的体裁以及科普文章常见的六种形式。 This talk describes what a genre of articles is and what six common forms of popular science articles ar
机器翻译利用汁算机模拟人的翻译过程,是一种智能处理过程,由于计算机本身没有自动思维能力,很大程度上靠人提供的一套推理机制及巨型的浯料库进行工作。类似下图: Machine
“大禹”之“禹”,金文作(?),《说文》释:“虫也。”千百年来为人们所顶礼膜拜的治水英雄怎么会是一条“虫”呢?其实,如果我们了解古代神话人物的得名常例,也许就不会对此大
在州委召开全州“三严三实”和“忠诚干净担当”专题教育活动动员会后,州委党校高度重视,及时召开校党委会议,传达学习州委会议精神,统一思想,提高认识,结合党校实际认真安排