Choosing & maintaining mice for type 2 diabetes and obesity research
Factors to Consider when Choosing Diabetes and Obesity Mouse Models
To choose the most appropriate model(s) for type 2 diabetes and obesity research, many factors need to be considered, including the following:
- Genetic nature of the phenotypes. The diabetic and obesity phenotypes of different models are very dependent on the genetic background of the mice. The diabetic and obesity phenotypes can be either monogenic or polygenic. For example in some models the diabetes is polygenic and the obesity is monogenic.
- The environmental stimulus for the phenotypes. The diabetic and obesity phenotypes develop spontaneously or are environmentally induced (e.g., by diet, chemicals, surgery, or housing conditions).
- Sex in which the phenotype develops. In some models, a phenotype develops in only one sex or much more dramatically in one sex. Additionally, though a phenotype may develop in both sexes, past research may have focused on only one sex. Generally, male mice are more severely affected by type 2 diabetes than female mice, and they are used exclusively in diet-induced diabetes studies.
- Degree of model characterization. Diabetes and obesity are more thoroughly characterized in some models (e.g. C57BL/6J DIO ob/ob and db/db mutants) than in others.
- Onset. Phenotype onset varies depending on the model and the genetic background.
- Severity. The severity of the phenotype is different for each model, and in the case of monogenic obesity mutants this is highly dependent on the genetic background.
- Associated phenotypes. Associated phenotypes, such as the integrity of the leptin/leptin receptor axis, lifespan, fertility, and the development and/or severity of hyperinsulinemia, insulin resistance, glucose intolerance, hyperglycemia, islet atrophy, hypertriglyceridemia, hypercorticism, hyperphagia, thermoregulatory defects, and organ-specific diabetic complications, vary among models and inbred strain backgrounds.
- Compound dosing method accepted. In some strains, such as NONcNZO10/LtJ (004456), strong stress responses to oral administration of compounds by gavage produce very high placebo effects.
Many strains of obese mice are sensitive to stress. To keep stresses at a minimum, try the following:
- Locate cages with obese mice that have thremoreglatory defects away from cold walls and drafts
- House polyuric mice at a low density
- Position cage racks a couple of inches away from a wall that may transmit disturbing vibrations (from equipment such as air exchangers)
- Ensure that food for hyerphagic obese models (especially if the food has been autoclaved) is not too hard (hard-to-chew food may lead to excessive tooth wear and weight loss)
- Place mouse cages away from a door or sink where there may be heavy traffic or loud noises
- Handle the mice gently, slowly, and quietly
- Change cage bedding at appropriate frequency (from once a week or, if the strain is diabetic and polyuric, as often as necessary)
- Resist the temptation to check on the mice too frequently
- Handle the mice with gloves (a fresh pair for each cage) or forceps
- Try using nestlets or Kimwipes® for nesting material
- Check water and food supplies frequently