Office of Laboratory Animal Resources, University of Colorado-Denver, Aurora, Colorado.
Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado-Denver, Aurora, Colorado.
J Am Assoc Lab Anim Sci. 2020 Nov 1;59(6):712-718. doi: 10.30802/AALAS-JAALAS-20-000005. Epub 2020 Sep 9.
Current methods for eradicating , such as depopulation, embryo transfer, and cesarean rederivation followed by cross fostering, are expensive, complex, and time-consuming. We investigated a novel method to produce immunocompromised offspring free of from infected NOD. Cg-PrkdcIl2rg/SzJ (NSG) breeding pairs. Adult NSG mice were infected with , paired, and randomly assigned to either a no-antibiotic control group (NAB, = 8) or a group that received amoxicillin-clavulanic acid (0.375 mg/mL) in their drinking water for a mean duration of 7 wk (AB group, = 7), spanning the time from pairing of breeders to weaning of litters. The AB group also underwent weekly cage changes for 3 wk after pairing to decrease intracage contamination, whereas the NAB mice received bi-weekly cage changes. Antibiotics were withdrawn at the time of weaning. All litters ( = 7) in the AB group were culture- and qPCR-negative for and remained negative for the duration of the study, whereas all litters in the NAB group ( = 6) remained positive. A single adult from each breeding pair was sampled at weaning and at 5 and 10 wk after weaning to confirm the maintenance of (NAB) or to diagnose the reemergence (AB) of infection. By the end of the study, infection had returned in 3 of the 7 (43%) tested AB adults. Our data suggest that metaphylactic antibiotic use can decrease viable organisms from adult breeder mice and protect offspring from infection. However, using antibiotics with frequent cage changing negatively affected breeding performance. Nevertheless, this technique can be used to produce -free NSG offspring from infected adults and may be an option for salvaging infected immunocompromised strains of mice that are not easily replaced.
目前根除 的方法,如人口减少、胚胎移植、剖腹产再衍生,然后交叉饲养,既昂贵、复杂又耗时。我们研究了一种生产免疫功能低下的 感染的 NOD.Cg-PrkdcIl2rg/SzJ(NSG)繁殖对的新型方法。成年 NSG 小鼠感染 ,配对,并随机分为不使用抗生素对照组(NAB,n=8)或接受饮用水中阿莫西林-克拉维酸(0.375mg/ml)治疗组(AB,n=7),持续时间为 7 周,涵盖从繁殖对配对到幼崽断奶的时间。AB 组还在配对后进行每周 3 次的笼子更换,以减少笼内 的污染,而 NAB 组则每两周更换一次笼子。在断奶时停止使用抗生素。AB 组的所有幼崽(n=7)的培养和 qPCR 均为 阴性,且在研究期间一直保持阴性,而 NAB 组的所有幼崽(n=6)均为 阳性。在断奶时,从每个繁殖对中采集一只成年动物进行采样,并在断奶后 5 周和 10 周时进行采样,以确认(NAB)或诊断(AB) 感染的重新出现。研究结束时,AB 组的 7 只成年动物中有 3 只(43%)被检测出再次感染。我们的数据表明,预防性使用抗生素可以减少成年繁殖鼠体内的存活 生物体,并保护幼崽免受感染。然而,频繁更换笼子会对繁殖性能产生负面影响。尽管如此,这种技术可以用来从感染的成年动物生产无 的 NSG 幼崽,并且可能是挽救不易替代的感染的免疫功能低下的小鼠品系的一种选择。