Modern production of laboratory animals

Published on February 11, 2015   48 min

Other Talks in the Series: Animal Models in Biomedical Research

0:00
Welcome to this lecture on Modern Production Methodologies of Laboratory Animals. My name is Martin Fitzner Toft, and I have over 10 years of experience in large-scale commercial breeding of mice and rats.
0:13
Looking at breeding mice and rats, it should be fairly simple, as depicted here. So the short version is that you bring a male and female together, you turn off the light, and something happens. And all of a sudden, you have a lot of pups. But that's only the short version.
0:29
If we're looking at how laboratory animals are used, they are very complex machines actually, or equipment. So if we're looking at the researchers' needs in a more generic way, what are they looking for? They're looking for correction and exact results, reproducible results. They would like to have high sensitivity and specificity. It should be a documented technique, or methodology. And they want predictive results. And if you're looking at that-- and that's actually regardless of the species used-- those are highly influenced by microbial and genetic quality when using laboratory animals. So that's what I will spend some time on during this lecture. Naturally, with my background, it's highly focused on mine and rats, which are also the species most commonly used for research. But, many of the aspects that I mentioned here is also applicable to other laboratory species to varying degrees.
1:34
If we're starting with first looking at the microbial quality, this is just an example. This is mouse hepatitis virus, also known as MHV. It's coronavirus. And on the left, you see some histopathological changes as a result of MHV. But those are only the direct effects on the animals. If we're looking at other areas where mouse hepatitis virus might interfere with research, it is known that it severely effects the immune system, resulting in a chronic immunodepression. It also alters the hepatic enzyme activity, which naturally, if you're looking at pharmical metabolomics, you have a problem if the enzyme activity is not normal. You can see procoagulant activity, anemia, leukopenia, and thrombocytopenia. It also increases the susceptibility to other pathogens as a result of the chronic immunodepression. It even can cause a rejection of xenograft tumors. But it can actually also be a disease model. So it's very important that, when you're looking at microbial quality in the animals, that you know which agents are there and how they might affect your research.
2:42
If we're looking at the microbial quality, it can be achieved through rederivation- I'll get back to that. It can also be maintained by using barrier techniques, also known as bioexclusion, and it can be monitored through extensive health monitoring.
3:00
Rederivation- that's the first step. How do we achieve clean animals? Embryo transfer is a well-proven technique to achieve clean animals. So basically, that means that you have unclean embryo donors that are mated. Then you have a set of "clean" recipients that are mated to vasectomized males to induce pseudopregnancy so that they are ready to receive the embryos at the stage that they will be implanted. Then you harvest the embryos from the donors, and you surgically implant them into the clean recipients.
3:34
So looking at this as just a drawing of how you do it. Naturally, this is very small, especially in mice. So it's done under a microscope. If you have two-celled embryos, you implant them into the oviduct. If you culture them to blastocyst stage, you will implement them in the uterine horn.
3:53
Barrier systems are needed in order to maintain clean animals, free of microbial agents that can be problematic. This is just a schematic drawing. This can basically be applied to any type of barrier. This represents a physical barrier, meaning a room. For instance, on the left you have a personnel lock where the people going into the room-changes follow the procedures that have been implemented. You have a chemical lock where you enter different objects. It could be cages, or it could be diet- anything that cannot be autoclaved will be exposed to a chemical disinfectant, a sterilant, and then be entered into the barrier. The autoclave is the method of choice to get in consumables, cages, all types of equipment into the barrier. You can really expose the things to high temperatures, high pressure, and thereby achieve maximum kill of microbial agents. But naturally, you have other entrances into a barrier room. You need to get air in there so you need to focus on filtering the air or treat it in some other way that reduces the microbial load, or even remove it. The water can also be a source of bacteria, especially and naturally, the drains. Most drains are not very clean. There also other rodent species living in the sewage system, and you definitely do not want those to get mixed in with your population inside the barrier. But it can also be insects getting access to the barrier, which can act as fomites and bring in unwanted agents.
Hide

Modern production of laboratory animals

Embed in course/own notes