Should You Breed or Buy Your Rodent Models?

Many research investigators are faced with a decision: should they buy laboratory rodents from a commercial vendor or produce them from an in-house breeding colony? There are many factors to evaluate before the decision to "breed vs. buy" can be made.

When You Must Breed

There are some situations in which you must breed your own mice or rats. The most common situation is use of a genetically engineered model (GEM) that is not available from a commercial source. Experiments which require embryos, fetuses, neonates, or maternal/intergenerational effects may also require in-house breeding. Strict control of the microbiome may be another reason to breed at your facility, though understand that simply breeding in the same location may not be sufficient to control the microbiome over time.

When the Answer Isn't Clear

Outside of the situations described above, the right choice may not be obvious. Factors to consider when making this decision include: quality, expertise, animal welfare, space constraints, microbiome, licensing, timeline, and total cost of production.

The following are a few questions to address before an informed decision can be made:

Are the rodents available from a commercial vendor?

If the answer is yes and the rodents are available at the sex, quantity, health standard, and frequency needed, the calculation for the cost to purchase is very straightforward: first, multiply the number of rodents you will need by the sales price. Then, factor in the price of shipping the animals to your facility. This is often the easiest and generally most cost-effective solution.

If the answer is no, you have two options:

Is it legally permitted to breed the rodents in-house?

It is imperative to know what the legal stipulations are for conducting in-house breeding of your desired model. Virtually all GEMs are produced and distributed under rights to patents and intellectual property licensed from various institutions. These rights are owned by the developing institution and licensed by commercial animal model providers. Inventing institutions and commercial providers distribute the models to researchers under material transfer agreements (MTAs) or other licenses, each of which have unique restrictions. Some of these agreements permit breeding, while others do not. Breeding rights may be available for a fee that can range from hundreds to thousands of dollars. Use of a model within the terms of your agreement is critical; breaching agreement terms can expose you and your institution to significant liability.

How large of a breeding colony is needed?

If the rodents aren't available as needed to meet your study goals from a commercial vendor, or you want to compare the cost for in-house breeding, you must answer the following questions to determine the size of breeding colony required, which in turn determines how many rodent cages are needed:

For outbred models, the complexity can be significant as outbred models are usually mated to maintain maximum heterozygosity, requiring a large colony size. Heterogeneity in outbred lines leads to increased variability in study results where, on average, more animals will be needed to detect treatment effects. Again, Russell and Burch's 3Rs should be considered.

What is the cost differential between buying or breeding?

Based on the factors noted above, let's review a simple example to determine if you should breed in-house or buy commercially.

Your research requires use of GEM line X. These are commercially available from a provider for $156/mouse.

You need 40 female mice at 9 weeks of age every month for at least one year. Your research is very sensitive, and only animals with a very tight age range (single week of birth) can be used. The provider's health standard is acceptable and the provider is willing to offer a breeding agreement for $4,000 annually.

Fortunately, the breeding performance of this model is known and it has a cage efficiency index of 2.00 (this means it takes 2.00 mouse cages to produce one mouse per week). To provide 40 F per week we must produce a total of 80 (40 M & 40 F) mice per week. Multiply 80 mice times the cage efficiency index of 2.00 and the colony will require 160 mouse breeding cages. There will also be a need for additional post-wean holding cages to allow the mice to age to 9 weeks. Housing 5 F/cage for 5 additional weeks will require 40 more cages. This brings the total cage need to 200.

The colony must produce the required number of needed mice each week to ensure availability due to the variable and unpredictable nature of breeding. This means you will need to produce 280 un-needed mice per month (40 M week #1, 40 F & 40 M weeks #2-4) to ensure you have 40 F at 9 weeks of age per month for your study.

Your vivarium manager has confirmed that there is space available for 200 cages and the weekly cage rate is $12.50. The caging cost for your colony per week is $2,500 (200 x $12.50). This translates to $130,000 annually; add in the breeder agreement fee for a total of $134,000. Keep in mind that genotyping costs may also be involved. Your annual mouse need is 480 F (40 / month x 12 months). The cost per mouse from your in-house breeding colony is $280 versus the commercially available price of $156 ($74,880 annually, plus transportation costs).

If you can expand the age range or use either sex, the equation changes, and the actual cost to produce in-house may become more competitive. However, you still must consider additional factors before making the decision.

Do you and the staff in your institution's vivarium have the expertise to breed the needed rodents?

Successfully maintaining a productive breeding colony is not easy. The perception that you can simply throw a few rats or mice into a cage and you'll have offspring in three weeks is a misconception.

There are many factors that can negatively impact breeding efficiency. A few examples of factors that must be considered are provided below:

How might genetic drift affect my experiment and can I control it effectively?

Genetic drift is unavoidable, but strategies exist to mitigate its impact. Commercial providers maintain pyramid colony structures for inbred strains, with periodic refreshing of the foundation colony from cryopreserved stock to eliminate the accumulation of mutations over time. For inbred GEMs, either periodic recovery from cryopreserved stock or periodic backcrossing to the inbred strain of interest can reduce accumulated drift. The strategies required to minimize drift may be beyond the space and cost constraints of many facilities.

Does your institution have the skills and equipment available to genotype the animals?

Assay development can be time-consuming and frustrating. The capital cost of acquiring the required genotyping equipment can be very high. There are several high-quality companies that you can outsource your genotyping needs to if needed. Transnetyx is a reputable provider of genotyping services. Keep in mind the cost of equipment, reagents, supplies, labor, and time commitment for this process. A method of record-keeping must also be considered to ensure the correct genotypes are identified, and lineage can be traced back if necessary. All assays used must appropriately distinguish between different lines in a room to prevent genetic contamination. If you rely on generic assays that detect cre or neomycin cassettes, you will not be able to detect accidental mis-matings if they occur.

Do you have time to wait for the rodents to be bred in-house?

Generally, you should calculate that it will take approximately three months per generation. If you only have a few animals to start the colony, you will need to breed them to produce enough breeders to meet the cohort size of your experiments. This could take several generations. The smallest cohort could take 6 - 9 months to generate. Your colony may not easily be able to accommodate changes to the design of a study, such as adding in another treatment arm or dose. If working with a breeding provider, they will offer in vitro fertilization options to reduce timelines such that large study cohorts can be generated from 1-2 donor males in as little as 3 months. Timeline and flexibility is a huge advantage when sourcing animals from a commercial provider.

Is there an "opportunity cost" with using your and/or your staff's time breeding mice?

Is your time is better spent on actual research rather than managing an in-house breeding colony? Could delays associated with in-house breeding prevent you from getting proof of concept data for grants in a timely fashion or prolong publication timelines? Successful colony management requires skill and dedication, and there is always a resource trade-off to consider.

As evidenced in this discussion, it isn't an easy decision to choose between buying your research rodents or producing them in-house. The default assumption that it is less expensive to breed in-house must be examined rigorously, with a full understanding of the true costs and time required.