Working with diabetic mice presents several challenges. Here we point out the 10 most recommended Do’s and Don’ts so you can streamline your experiments, reduce variability and get consistent results when working with the most popular mouse models of diabetes.
Diabetic mice drink more water than wt mice.
Obese mice have a harder time to access the feeders and water supply compared to controls.
If you are working with hyperphagic mice such as ob/ob and db/db strains.
Mouse models of diabetes typically urinate more than wt mice.
Consider using cellulose based bedding such as ALPHA-Dri® for superior absorbency and ammonia control when working with polyuric strains.
Stressing them out may delay the onset of the disease and make the phenotype less severe.
For several mouse models of diabetes, the course of the disease is age-dependent.
Often the penetrance and the disease severity differ between males and females. For example at 20 weeks of age, only ~50% of NOD/ShiLtJ (stock # 001976) males will actually become diabetic, compared to 90% of age-matched females from the same strain.
Include extra mice to account for non-responders and outliers. Make sure that you have enough mice (n) that express a specific phenotype to ensure statistical significance of your experiments.
Asynchronous studies are often required for biological model of diabetes, but induced models (such as STZ ablation of beta cells) can often be run synchronously.
Diabetic phenotypes in mice are highly sensitive to distress. Stress levels may interfere with gaining body weight and developing hyperglycemia (this is extremely important for lep ob/ob and lepr db/db mice models of Type 2 diabetes). Taking extra precautions will maximize phenotypic stability and minimize mouse to mouse variability.
Plastic Mouse Houses or Igloos, soft fibrous nesting material, chewing materials such as Nylabones®, minimize distress and promote normal behaviors.
The presence of pathogens can delay or prevent the development of diabetes (this is extremely important when working with NOD mouse colonies).
The best time to measure high glucose levels is early in the morning (after a good night of feeding and fun).
Glucose levels vary depending on the blood collection site (retro-orbital vs tail vein).
Start out with extra mice so you can compensate for this.
Fat diabetic mice have other activities in mind (eating!). Plus, homozygous mice are infertile.
As Type 2 db mice become obese, it is helpful to place additional food on the floor of the cage to ensure that the mice will have easy access to it, even when they become really heavy.
The acclimation period is critical. How long the acclimation period needs to be can vary, but it may take as long as 2 weeks. During this acclimation period, the mice are able to recover from travel, adjust to the new environment.
For example mice with the Lepr<db> mutation in the C57BLKS genetic background (stock # 000642) DO progress to the late stages of diabetes with the development of islet atrophy. They are severely hyperglycemic and become progressively worse over time. On the other hand, mice with the same mutation on the C57BL/6J genetic background (stock # 000697) DO NOT progress to the late stages of diabetes such as the development of islet atrophy. These mice are useful as a transient model of early stages of diabetes and their phenotype normalizes by 14-16 weeks of age.
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