Should You Breed or Buy Your Own Rodent Models?


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

Following are a few questions and considerations that must be addressed 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 status, and frequency needed, the calculation for the cost to purchase is very straightforward: multiply the number of rodents you will need by the sales price. You may also need to factor in the price of shipping the animals to your facility. This is the easiest and generally most cost-effective solution.

If the answer is no, you have two options:

  1. Breed them in your facility vivarium.
  2. Outsource the breeding to a commercial provider of animal model breeding solutions.

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 most rodent strains. Virtually all rodents are produced and distributed under rights to patents and intellectual property licensed from various institutions. These rights are owned by the developing institution purchased by commercial animal model providers.

Often, an annual breeding agreement must be issued, and the agreement is normally accompanied with a fee that can range from hundreds of dollars to thousands. Be sure to know the legal obligations for the rodents you wish to breed.

How big 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:

  • How many rodents are needed for the study? This is step one in determining colony size. The required quantity of rodents sets the baseline for establishing the number of needed active breeders. You will also need to consider generating additional rodents beyond what is needed for the study to be retained and used to replace aged breeders in the colony as they become non-productive.
  • At what frequency will the rodents be needed? The frequency of the demand must be compared to the litter delivery frequency. If the frequency between study cohorts is less than every 3-4 weeks, the number of required breeders increases significantly due to gestational and weaning time needs.
  • What is the required age of the animals needed? This sounds like a simple question, but the cost of production can increase dramatically based on the need. Does the research require a very tight animal age range, or can a larger age range be used? A very tight age range will require more breeding females to ensure the required number of animals are born on the desired date.
  • What sex of rodent is needed? If either sex can be used the size of your colony can be cut in half. If only one sex can be used, you must double the colony size and understand the animal obsolescence (waste) of euthanizing the un-needed sex. The need for a single sex also requires you to ask the question of whether the euthanasia of the un-needed sex is necessary and ethically appropriate based on Russell and Burch's 3Rs. Additionally, it is prudent to consider the NIH Policy on Sex Balance when planning your studies. One ethical advantage of buying from an approved vendor is that often the un-needed sex can be utilized by other researchers.
  • What is the breeding performance? How many actual breeders needed will require knowledge of the fecundity of the background strain or prior actual performance. To calculate breeding colony size, you will need to know the average number of pups weaned per litter and litter weaning frequency.
  • What is the required health status of the rodent? If you require a higher health standard than your vivarium can maintain, you may need to look at an outside provider. As a rule, the higher the needed health standard, the higher the cost of production.
  • What is the mating format required for the required animals? Are the rodents inbred or outbred? Both breeding schemes have very specific requirements to maintain genetic integrity. For an inbred traditional strain, or an inbred genetically modified strain that is bred homoxygous x homozygous for the modification(s) of interest, all offspring will have the desired genetic status and can be used in the research. This reduces the animal obsolescence (waste). If the breeding scheme is heterozygous x heterozygous or contains multiple genetic modifications then Mendelian or non-Mendelian inheritance patterns should be anticipated where the actual usable offspring with the desired genetic status is reduced significantly and causes waste of the non-desired genotypes that are produced. 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 lend 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. Keep in mind that breeding schemes that require genotyping add cost.

What is the cost differential between buying or breeding?

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

Note: The following example is for demonstration purposes only. Actual costs and breeding permission must be confirmed with the providers.
Your lab would like to do immunological research and has chosen the genetically modified mouse model Abb (H2-Ab1). It is commercially available from Taconic Biosciences as Model ABBN12 at $156 / animal.

You will require 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. Taconic's Murine Pathogen Free™ health standard is acceptable, and Taconic 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 to 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 euthanize 280 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.

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).

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 ask a couple questions before making the decision.

Do you or 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:

  • Stress — Stress on a breeding colony can result in lost litters, cannibalized pups, in utero resorption or abandonment of the litter. Stress comes in many forms such as: frequent cage changes, environmental swings of temperature or humidity, changing of the animal technician, light cycle, male breeder rotation, noises and vibrations, unusual odors or pheromones from other cages, to name just a few stressors.
  • Lethal Genetics — When using genetically engineered models, it's important to ensure the desired genotype does not confer lethality. It isn't uncommon for some strains to have a high fetus mortality that results in small litter sizes.
  • Improper Breeding Environment — Rodents are shy. An open cage with no place to hide or nest may reduce performance. Providing a place to breed like a Shepard Shack® and/or adding nesting material like Nestlets may improve breeding.
  • Improper Nutrition — The rigors and nutritional needs of gestation are significant. The proper food should be provided to ensure good production. Purina and other food suppliers have specially formulated "Breeder Chow" that often contain higher fat levels that may improve breeding. Note: Higher fat breeder chows may not be appropriate for use in all strains. For example, high fat diets may induce undesired obesity in models on the C57BL/6 background.
  • Too Much Light — Rodents are nocturnal and most of the breeding activity will occur with the lights out. Make sure the vivarium maintains a light/dark cycle of at least 10 hours of uninterrupted darkness.

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.

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. 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.

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

Basically, you should ask the question of whether your time is better spent on actual research versus time spent managing an in-house breeding colony.

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

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