Easier Said than Bred: 4 Considerations for Breeding Laboratory Mice

In vitro Fertilization
Have you ever had a mouse infestation in your house? This is a pesky problem that can prove difficult to resolve. After all, they breed like... well, mice. So why is it so difficult to breed laboratory mice?

Laboratory mice are purpose-bred for specific phenotypes or traits, not to optimize litter size. Quite often, fecundity is sacrificed to attain traits desired for laboratory mouse studies, or breeding is affected negatively by genetic engineering. This can present costly headaches for cohort development.

If you are looking for Comprehensive Mouse Breeding 101, you will not find it in this Insight. These are the four main factors to consider if you are a novice when it comes to breeding laboratory mice for your study cohorts.

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.

3. Don't Reinvent the Wheel

Laboratory mouse breeding is a mature discipline, with a number of publicly-accessible sources of information on your strain.

First, a simple web search for laboratory mouse breeding standard operating procedures (SOPs) will bring back results from reputable research laboratories providing SOPs and videos.

You can even search for information for your specific background strain of your mouse. Lee Silver's well-known book Mouse Genetics (Oxford University Press, 1995) provides a table of reproductive traits for 12 popular inbred strains*. See below:

Strain Productive matings Weeks at first mating Litter size Number of litters Relative fecundity Response to superovulation
129/SvJa 75% 7.9 5.9 4.1 18.1 High
A/J 65% 7.6 6.3 2.9 11.9 Low
AKR/J 84% 6.6 6.1 2.2 11.3 -
BALB/cJ 47% 8.0 5.2 3.8 9.3 Low
C3H/HeJ 86% 6.7 5.7 2.9 14.2 Low
C3H/HeOuJ 99% 5.9 6.4 3.7 23.4 -
C57BL/6J 84% 6.8 7.0 4.0 23.5 High
C57 BL/10SnJ 67% 7.7 6.3 2.8 11.8 -
CBA/CaJ 96% 6.4 6.9 2.7 17.9 High
DBA/2J 75% 7.4 5.4 3.9 15.8 Low
FVB/N >90% - 9.5 4.8 41.0 Moderate
SJL/J 72% 7.4 6.0 3.1 13.4 High

4. An Alternative to Breeding Laboratory Mice

A better question to ask yourself is, why do I need to breed the model myself? The answer is, you don't.

There are a number of ways to develop the cohort sizes you need at the specifications required:

  • Perhaps a collaborator is already breeding the strain? Maybe they would be willing to provide you study cohorts.
  • Commercial providers have optimized conditions for breeding laboratory mice of many different strains. You can readily source most common strains of mice, often at a lower cost than you can achieve in your own animal facility.
  • Unique genetically engineered strains can be outsourced through a contract breeding option. With experience breeding 1000s of different strains, outsource providers can often optimize breeding plans to improve overall breeding performance. They have many tools available to them, such as rapid expansion, which takes advantage of assisted reproductive technologies like in vitro fertilization to develop large cohorts of hard-to-breed mice. (In some cases, very limited natural breeding takes place and study cohorts are developed mostly through IVF). While the up-front price might seem high, in the end it is less expensive than maintaining a large breeding colony with poor reproductive traits.

If this is your first foray into breeding laboratory mice, keep these four considerations in mind. Any one of them might caution against setting up an independent breeding colony - or land you in front of your boss, with an incomplete study to answer for.

*Matings are considered "productive" if any offspring at all are born. "Weeks at first mating" refers to the age at which the first "productive" mating occurred; it is estimated by subtracting 3 weeks from the age of the parents at the first birth. "Relative fecundity" is obtained as the following product: (productive mating frequency) X (litter size) X (number of litters); the value obtained is a measure of the overall fecundity of the strain. Data for all strains other than FVB/N are extracted from the Handbook of Genetically Standardized JAX Mice (Green and Witham, 1991). Data for the FVB/N strain are extracted from a publication by Taketo and colleagues (1991).