Diet-induced obese (DIO) C57BL/6J (B6) mice are a popular pre-type 2 diabetes and obesity model. This is because B6 mice placed on a high-fat diet display phenotypes similar to pre-diabetic humans and patients with metabolic disease, including increased weight gain, elevated blood glucose and impaired glucose tolerance. While they are a great model, some mice within a given study group may stop gaining weight or experience weight loss that in turn impacts glucose metabolism. In fact, there are several factors that result in milder phenotypes in DIO mouse models. Here we share our tips and tricks that will help you promote the stability and consistency of DIO-related phenotypes.
JAX DIO mice (stock # 380050) are fed a 60% high-fat diet D12492, which doesn’t have a long shelf life at room temperature. It is highly recommended to keep the food refrigerated in the short-term and frozen for long-term storage. It is best if you change the food in the hopper once per week to avoid spoilage. We actually place frozen food in the hopper when we clean the cage. Make it a point to place the older food from the hopper onto the floor of the cage to ensure mice have access to food at all times, to promote weight gain, especially when they get really large and have difficulties rearing up to the hopper.
Water should be accessible to mice at all times. If your facility has an automatic water supply, make sure to provide mice with a water bottle during the first week after arrival while they get used to the new watering system. Having easy access to a plentiful water supply is critical to keeping the mice well hydrated and for maintaining increased body weight.
We only distribute DIO mice that are above specific age-dependent weight thresholds. A table is available with data regarding the minimum body weights for DIO mice at shipment. During transit, it is relatively common for DIO mice to lose some weight, but they typically gain it back a week or two after arrival. Please note, however, that the animals’ weights may never catch up to what they would have been had they not been shipped. Therefore, always plan for a 1-2 week acclimation period whenever you have DIO mice shipped to your facility.
Reducing stress helps DIO mice gain and maintain the proper weight. Diminish the possibility of fighting by keeping mice from different shipping containers separate.
• If possible, co-house DIO mice that were weaned together. Keep in mind that singly-housed mice burn calories to keep warm. Mice housed individually may not thrive as well as those that are group-housed.
• Remember to handle mice gently, slowly, quietly and as little as possible.
• Use enrichment materials such as Shepherd Shacks, Nylabones and/or soft fibrous nesting materials (e.g. Nestlets).
We do not recommend corn cob bedding for DIO mice because the mice tend to eat it and get full, while not deriving any calories from it. This may result in the animals not eating as much of the high-fat diet and not gaining weight as expected. At JAX, we maintain our DIO mice on a 1:1 blend of aspen wood chips (PJ Murphy) and aspen shavings. We supplement shavings with extra-absorbent material such as Alpha-dri. We do not recommend that you use Alpha-dri only, because the mice benefit from moving the chips and shavings around and building nests. Such behavior can help to reduce stress and promote weight gain. Consider using additional bedding to ensure that chubby mice can easily reach food and water and maintain thermostability.
The best time to measure high glucose levels is early in the morning. Because the mice are most active and feeding at night, glucose levels in the early morning will be non-fasted. Regardless of when you measure glucose levels in your mice, it is most important to sample the mice at the same time of the day throughout your study to promote more consistent data.
We recommend ordering between 5-10% extra mice for any given study, because in our experience some DIO mice just don’t regain weight after the acclimation period. If you are initiating the placement of mice on a high-fat diet at your facility, always include 10% more mice than absolutely needed for your study groups because some mice simply do not respond to the diet and need to be excluded from your research.