1. Strain Considerations
First and foremost are strain considerations. Inbred mice such as C57BL/6 are moderate breeders compared to the outbred Swiss Webster mice.
If you are using a hybrid or outbred strain, you can expect consistent litter sizes of eight or more. Contrast that with the C57BL/6 inbred strain, which might only deliver three-to-four mice per litter, or genetically engineered mice, which often deliver triplets at most.
Add in cohort specifications, such as sex, and your three-to-five mice can become one mouse.
And that is just litter size! There is usually some attrition before weaning, and even a moderate rate can decimate a cohort of genetically engineered mice. What looked like a good study on paper can quickly turn into frustration and wasted time and money.
2. Environmental Factors
There are other factors which affect breeding, including cage and bedding type, diet formulation, light cycle, temperature and humidity ... and, of course, the people who handle your mice on a regular basis.
If anyone of these factors is out of specification or does not support breeding your specific strain of mice, you might struggle to reach minimal cohort sizes. Typical research animal facilities are set up to breed a wide variety of research animals and cannot be altered to optimize breeding for a single mouse line.