Model Organisms in Environmental Health

By Amanda Buerger, Sara Humes, and Alexis Wormington

​One aspect of environmental health revolves around understanding how changes in the environment, whether human or naturally-caused, may impact the health of global populations and ecosystems. Model organisms are non-human species used to understand biological processes in a laboratory setting. Model species should be affordable, easy to keep in a laboratory setting, and an appropriate species to study in the context of the scientific question being asked. In this post we’ll go over three model species that are commonly used in the field of environmental health, why we use them, and their advantages and disadvantages as models.
 
Daphnia
 
Daphnia, commonly known as the “water flea”, are a genus of aquatic crustaceans used very commonly in basic toxicological studies. Daphnia species are favored because they are very inexpensive, low maintenance animals with a short life cycle. Since they are invertebrates, the ethical and legal requirements for their use are minimal compared to more complex models, such as non-human primates and rodents. Daphnia are unique because they typically reproduce asexually, meaning all of their offspring are genetically identical to the mother. They can produce over 100 eggs at a time, and reproduce approximately every two days! Because of their rapid and unique life cycle, these organisms are valuable to use in both reproductive studies and toxicity tests. Daphnia studies often provide the foundation for the basic toxicity of chemicals.
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Like with any model, using Daphnia comes with its disadvantages. Since Daphnia are invertebrates, their application to human health is very limited, as mammals and invertebrates have vastly different molecular, chemical, and physical processes involved in biological function. Additionally, their brief life cycle makes them impossible to use in long-term studies, which restricts the kinds of questions we can ask and answer using Daphnia as models.

Figure 1: Three commonly used Daphnia models. Daphnia magna (left), Daphnia pulex (middle), and Ceriodaphnia dubia (right).

Zebrafish
 
Alternatives to invertebrate and mammalian models are fish, which are generally smaller, cheaper, and easier to care for than rodents, non-human primates, and other higher level models. There are several species of model fish, from tiny minnows, to predatory trout and bass, to one of the most common fish models - zebrafish. While not as closely related to humans as mammals, fish share several characteristics with humans, including conserved biochemical processes in the brain, gastrointestinal system, and cardiovascular system. In the case of the zebrafish, the gut is similar to that of humans, and therefore these fish are used to study diseases related to the intestinal tract, such as obesity and inflammatory diseases. Due to increased funding of studies using zebrafish, this inexpensive model organism is becoming more commonly used in scientific research.  Because of their prolific use, the genome of the zebrafish has been sequenced, and scientists are able to utilize this knowledge to create zebrafish that are useful for their studies.  Finally, the development of zebrafish is easy to monitor, as the embryos and larvae are transparent.

As with any model, there are limitations to its use. Most fish species experienced a duplication of genes millions of years ago, and therefore generally have two functioning genes for each one human gene. Additionally, there are some other differences between fish and humans, such as the respiratory tract and the presence of two pairs of kidneys in some fish, each with distinct function.  Fish are also housed together in tanks, and there is uncertainty as to whether the whole tank should count as one sample or if each fish in a tank should be considered individually. As we understand more about zebrafish, we will be able to evaluate the use of this organism as a model for different human diseases.

Figure 2: An adult zebrafish (left) and a larval zebrafish that has been modified to express green fluorescent protein (right).

Rodents
 
The most commonly used and well-established mammalian models in scientific research are the mouse and rat. Compared to other mammalian models, such as non-human primates, livestock, and cats, mouse and rat models are less expensive and easier to house. Some advantages of using mice and rats for toxicological research include their short lifespan, small size (for easier care and housing), short gestation times for large litters, and genetic and biological similarity to humans. Approximately 95% of some 30,000 genes are shared between mice, rats, and humans, resulting in a lot of biological resemblance. This similarity makes rats and mice a good stepping stone between lower models and humans. Additionally, we have fully sequenced the genome of the mouse and rat, making it easier to focus on a particular gene of interest for a research project. Knowing the full genome allows researchers to create genetically engineered rodents that are missing or have an excess of certain genes or proteins to shed light on their function and role in response to toxicological stressors. Research rodents are also bred so that two animals of the same strain are nearly genetically identical, eliminating much of the variability between individual animals.
 
Despite these advantages, there are some disadvantages to using rodent models. Rodents and humans still have some fundamental differences in physiology, limiting their application to humans in certain cases. For example, rodents cannot cough, so study outcomes related to the respiratory system may be different than those observed in humans. Since rodents are mammals, there are also many more regulations, training, financial resources, and ethical considerations required to work with them compared to non-mammalian models. Regardless, rodents are a well-respected, frequently used model in all areas of scientific research, and their use has led to many scientific advancements. 

Figure 3: Commonly used mouse and rat strains for toxicological research. Top row: BALB/c mouse (left) and C57BL/6 mouse (right). Bottom row: Sprague-Dawley rat (left) and Wistar rat (right).