Pfizer Worldwide Research, Development and Medical, Comparative Medicine, Cambridge, Massachusetts.
J Am Assoc Lab Anim Sci. 2022 Sep 1;61(5):432-440. doi: 10.30802/AALAS-JAALAS-22-000028. Epub 2022 Aug 31.
Maintenance of an appropriate microenvironment for rodents used in research is of paramount importance because changes in environmental parameters such as O₂ and humidity can influence animal health and welfare and potentially alter research results. Here we evaluated the microenvironment of mouse and rat disposable cages after removal from mechanical ventilation in order to guide recommendations for their use. Cages with sealed IVC lids, unsealed lids (partially ajar), and lids without the exhaust filter (for rats) or static lids (for mice) were removed from the ventilated rack and were thereafter monitored CO₂, O₂, and NH₃ levels. For mice, effects were investigated under both standard (set point of 72°F/22°C) and thermoneutral (set point of 82°F/28°C) temperatures. When IVC with sealed lids and group-housed C57BL/6J male mice were removed from ventilation under standard temperatures, CO₂ started at 6,600 ± 265 ppm at 0 h and rose to 42,500 ± 7,263 ppm at 1 h, with mice showing a visibly elevated respiratory rate in 1 of the 3 cages; CO₂ stabilized at 26,150 ± 3,323 ppm at 8 h. In contrast, CO₂ levels in cages with single mice were stable after 1 h (1,350 ± 409 ppm at 0 h, 9,367 ± 802 ppm at 1 h, and 8,333 ± 1,115 ppm at 8 h). Findings were similar at thermoneutral temperatures: sealed group-housed mice cages started at 3,617 ± 475 ppm at 0 h and rose to 39,333 ± at 5,058 ppm at 1 h, whereas sealed cages with 1 mouse started at 1,117 ± 247 ppm at 0 h and were 7,500 ± 1,997 ppm at 8 h. IVC with sealed lids and pair-housed Crl:CD(SD) female rats rose to 48,000 ± 2,828 ppm CO₂ and over 70% humidity within 1 h. By 3 h, IVC with sealed lids and singly housed rats had 40,167 ± 5,132 ppm CO₂, and rats were displaying a visually elevated respiratory rate. O₂ levels had an inverse relationship with CO₂ levels. Removing the rat lid exhaust filter was not helpful. However, leaving the IVC lid ajar ameliorated the rise in CO₂ and fall in O₂ for both species. Therefore, IVC with sealed lids and group-housed mice should not be removed from ventilation more than 1 to 2 h; IVC containing pair- or singly-housed rats IVC should not be removed for more than 1 or 3 h, respectively. Whenever possible, such cages should be fitted with static lids, left partially ajar and monitored, or replaced on ventilation.
维持用于研究的啮齿动物的适当微环境至关重要,因为环境参数(如 O₂ 和湿度)的变化会影响动物的健康和福利,并可能改变研究结果。在这里,我们评估了从机械通气中取出的小鼠和大鼠一次性笼的微环境,以指导其使用建议。具有密封 IVC 盖子、未密封盖子(部分打开)和没有排气过滤器(大鼠)或静态盖子(小鼠)的笼子从通风架上取下,然后监测 CO₂、O₂ 和 NH₃ 水平。对于小鼠,在标准(设定点为 72°F/22°C)和热中性(设定点为 82°F/28°C)温度下进行了研究。当密封盖子的 IVC 和群养 C57BL/6J 雄性小鼠在标准温度下从通风中取出时,CO₂ 在 0 小时时开始为 6,600 ± 265 ppm,并在 1 小时时上升至 42,500 ± 7,263 ppm,其中 3 个笼子中的 1 个显示出明显升高的呼吸率;CO₂ 在 8 小时时稳定在 26,150 ± 3,323 ppm。相比之下,1 小时后,单只小鼠笼中的 CO₂ 水平稳定(0 小时时为 1,350 ± 409 ppm,1 小时时为 9,367 ± 802 ppm,8 小时时为 8,333 ± 1,115 ppm)。在热中性温度下也发现了类似的结果:密封的群养小鼠笼在 0 小时时开始为 3,617 ± 475 ppm,并在 1 小时时上升至 39,333 ± 在 5 小时时达到 39,333 ± 5,058 ppm,而密封的单只小鼠笼在 0 小时时开始为 1,117 ± 247 ppm,在 8 小时时为 7,500 ± 1,997 ppm。具有密封盖子的 IVC 和配对饲养的 Crl:CD(SD)雌性大鼠在 1 小时内 CO₂ 上升至 48,000 ± 2,828 ppm,湿度超过 70%。到 3 小时时,具有密封盖子的 IVC 和单独饲养的大鼠 CO₂ 水平为 40,167 ± 5,132 ppm,大鼠显示出明显升高的呼吸率。O₂ 水平与 CO₂ 水平呈反比。去除大鼠盖子排气过滤器没有帮助。然而,让 IVC 盖子半开可以缓解 CO₂ 的上升和 O₂ 的下降,这两种情况都有所改善。因此,不应将密封盖子的 IVC 和群养小鼠从通风中取出超过 1 到 2 小时;不应将含有配对或单独饲养大鼠的 IVC 从通风中取出超过 1 或 3 小时。只要有可能,这些笼子应配备静态盖子,保持半开状态并进行监测,或更换通风。