Brochu Catherine P, Winnicker Christina L, Provencher Anne L, Debien Elaine, Gariépy Sebastien, Gaskill Brianna N
Veterinary Care and Services Department, Charles River Laboratories, Montreal, Quebec, Canada;, Email:
Institute of Comparative Medicine, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, New York.
J Am Assoc Lab Anim Sci. 2018 Jul 1;57(4):340-349. doi: 10.30802/AALAS-JAALAS-17-000114. Epub 2018 Jul 5.
The provision of nesting material benefits mice by reducing cold stress, improving feed conversion, increasing litter size, and improving adaptive immunity. The effects of toxins are sensitive to environmental changes, and the introduction of novel items can alter results in some toxicologic studies. We hypothesized that nesting material would reduce stress and positively alter immunologic parameters in Crl:CD1(ICR) mice, thus changing typical results from a well-studied immunomodulating drug, cyclophosphamide. A 13-wk study assessed the following treatments in a factorial design (n = 4; 32 cages total): nesting (0 or 10 g) and drug (50 mg/kg cyclophosphamide or 10 mL/kg saline; IP weekly). Detailed examinations and body weights were recorded weekly, and nests were scored twice weekly. Fecal pellets were collected at 0, 4, 6, and 12 wk for analysis of corticosterone metabolites. At study termination, clinical pathology and immune parameters were collected, a necropsy performed, and lymphoid organs and adrenal glands were submitted for histopathology. All expected results due to cyclophosphamide were observed. Nesting reduced the proportion of mice with piloerection, and body weights were highest in saline-nested male mice. No differences in hematology, clinical chemistry, or absolute lymphocyte counts were observed. Corticosterone metabolites in all nested groups were not different from baseline levels but all nonnested groups had higher levels than baseline. Nested cyclophosphamide-treated groups had significantly lower corticosterone levels than nonnested cyclophosphamide-treated groups. This study illustrates that nesting material does not alter the results of a standard toxicology study of cyclophosphamide but alleviates study-related stress and improves mouse welfare.
提供筑巢材料对小鼠有益，可减轻冷应激、改善饲料转化率、增加窝仔数并提高适应性免疫力。毒素的影响对环境变化敏感，引入新物品可能会改变某些毒理学研究的结果。我们假设筑巢材料会减轻应激并正向改变Crl:CD1(ICR)小鼠的免疫参数，从而改变一种经过充分研究的免疫调节药物环磷酰胺的典型结果。一项为期13周的研究采用析因设计评估了以下处理（n = 4；共32个笼子）：筑巢（0或10克）和药物（50毫克/千克环磷酰胺或10毫升/千克生理盐水；每周腹腔注射）。每周记录详细检查结果和体重，每周对巢穴评分两次。在第0、4、6和12周收集粪便颗粒以分析皮质酮代谢物。在研究结束时，收集临床病理学和免疫参数，进行尸检，并将淋巴器官和肾上腺送去做组织病理学检查。观察到了环磷酰胺产生的所有预期结果。筑巢减少了竖毛小鼠的比例，生理盐水筑巢的雄性小鼠体重最高。在血液学、临床化学或绝对淋巴细胞计数方面未观察到差异。所有筑巢组的皮质酮代谢物与基线水平无差异，但所有未筑巢组的水平均高于基线。筑巢的环磷酰胺处理组的皮质酮水平明显低于未筑巢的环磷酰胺处理组。这项研究表明，筑巢材料不会改变环磷酰胺标准毒理学研究的结果，但可减轻与研究相关的应激并改善小鼠福利。
