Francis Freddy, Varankovich Natallia, Brook Byron, Amenyogbe Nelly, Ben-Othman Rym, Cai Bing, Harbeson Danny, Liu Aaron C, Dai Ben, McErlane Shelly, Andrews Kris, Kollmann Tobias R, Panigrahi Pinaki
Department of Experimental Medicine, University of British Columbia;
Department of Pediatrics, University of British Columbia.
J Vis Exp. 2019 Jan 27(143). doi: 10.3791/59074.
Adult mouse models have been widely used to understand the mechanism behind disease progression in humans. The applicability of studies done in adult mouse models to neonatal diseases is limited. To better understand disease progression, host responses and long-term impact of interventions in neonates, a neonatal mouse model likely is a better fit. The sparse use of neonatal mouse models can in part be attributed to the technical difficulties of working with these small animals. A neonatal mouse model was developed to determine the effects of probiotic administration in early life and to specifically assess the ability to establish colonization in the newborn mouse intestinal tract. Specifically, to assess probiotic colonization in the neonatal mouse, Lactobacillus plantarum (LP) was delivered directly into the neonatal mouse gastrointestinal tract. To this end, LP was administered to mice by feeding through intra-esophageal (IE) gavage. A highly reproducible method was developed to standardize the process of IE gavage that allows an accurate administration of probiotic dosages while minimizing trauma, an aspect particularly important given the fragility of newborn mice. Limitations of this process include possibilities of esophageal irritation or damage and aspiration if gavaged incorrectly. This approach represents an improvement on current practices because IE gavage into the distal esophagus reduces the chances of aspiration. Following gavage, the colonization profile of the probiotic was traced using quantitative polymerase chain reaction (qPCR) of the extracted intestinal DNA with LP specific primers. Different litter settings and cage management techniques were used to assess the potential for colonization-spread. The protocol details the intricacies of IE neonatal mouse gavage and subsequent colonization quantification with LP.
成年小鼠模型已被广泛用于了解人类疾病进展背后的机制。在成年小鼠模型中进行的研究对新生儿疾病的适用性有限。为了更好地理解新生儿疾病的进展、宿主反应以及干预措施的长期影响,新生儿小鼠模型可能更合适。新生儿小鼠模型使用较少,部分原因可归结为处理这些小动物存在技术困难。开发了一种新生儿小鼠模型,以确定早期给予益生菌的效果,并具体评估在新生小鼠肠道中建立定植的能力。具体而言,为了评估益生菌在新生小鼠中的定植情况,将植物乳杆菌(LP)直接递送至新生小鼠的胃肠道。为此,通过食管内(IE)灌胃法给小鼠喂食LP。开发了一种高度可重复的方法来规范IE灌胃过程,该方法能够准确给予益生菌剂量,同时将创伤降至最低,鉴于新生小鼠的脆弱性,这一点尤为重要。该过程的局限性包括如果灌胃不当,可能会导致食管刺激或损伤以及误吸。这种方法是对当前做法的一种改进,因为向食管远端进行IE灌胃可降低误吸的几率。灌胃后,使用针对LP的特异性引物对提取的肠道DNA进行定量聚合酶链反应(qPCR),追踪益生菌的定植情况。使用不同的窝仔设置和笼养管理技术来评估定植传播的可能性。该方案详细介绍了IE新生小鼠灌胃以及随后用LP进行定植定量的复杂过程。