What are common research models?

Scientists use a range of different model organisms, including animal models, to investigate research questions. Using animal models is critical to learn about diseases such as SLC13A5 Epilepsy. Scientists use animal models because they allow us to learn things we cannot learn from other methods. They also allow scientists to test potential new treatments to understand if the treatment would work in humans. Each animal model has its strengths and weaknesses. How do scientists decide which one to use? This article will review some animal models that are commonly used in research and why scientists may choose one over the other.

What models can be used to identify new drugs to treat a disease?

If a researcher is trying to learn about new drugs (compounds) to treat a disease, they may have thousands of compounds to test. How do you begin to test all these different compounds? A researcher would have to sort through many different compounds in a short amount of time. This process is often referred to as drug screening. Researchers look for a few different characteristics when choosing a model for drug screening.

Key characteristics for models for drug screening:

  1. Reproduce quickly
  2. Shows some of the symptoms of the disease being investigated
  3. Are easy to grow
  4. Low cost

Why are flies and worm models used for drug screening?

Some of the models that are useful for drug screening are fruit flies, also known as Drosophila melanogaster, and worms, also known as C. elegans. Even though they don’t look like humans, these models are useful for investigating diseases. For example, did you know that there are flies that lack the SLC13A5 gene?

Researchers may use flies or worms for research because they are:

  • Easy to grow
  • Fast to reproduce and mature
  • Low in cost to maintain as entire colonies
  • Models that have many genetic research tools available for studying them
  • Have less complex nervous systems (the connection of neurons throughout the body), but still have many underlying mechanisms and shared with humans

What models can be used to watch individual cells grow and develop?

Another common research question is: how do cells behave during a person’s development? This is particularly important for diseases that start early in life, such as SLC13A5 Epilepsy. For example, how does a neuron develop and make connections with other neurons? (Check out our Science Simplified blog about neurons here) To investigate this kind of question, a researcher may use a model that:

  • Grows and matures quickly
  • Has tools available to label individual cells
  • Is amenable to live imaging, or the ability to take pictures or movies in a living organism

Scientists often use powerful microscopes to zoom in on individual cells and track how a cell moves and behaves over time. One model that is often used to watch cells develop over time is the zebrafish model.

Zebrafish are often used for research because they:

  • Are optically transparent during early development
  • Develop quickly
  • Produce many offspring at once—there can be hundreds of zebrafish embryos from one mating
  • Have many tools available to individually label cells
  • Absorb drugs that are added directly to the water they swim in—they can be used for drug screens
  • Have many genes that are similar to humans

What models can be used to learn how individual genes affect different parts of the body?

Sometimes researchers want to learn which parts of the body are directly affected by a specific gene (the body’s recipe for making the proteins and factors you need to stay healthy). To answer this type of question, scientists often turn to rodent models, such as mice. Mice are one of the most common models. They share many similar genes to humans and are a common vertebrate model.

Part of why mice are helpful for scientific research is because of the robust genetic tools available for studying them. These tools allow researchers to delete specific genes from (1) the entire genome or (2) from specific cell types in the mice. Using these tools, a scientist could remove a specific gene from the entire genome. When a research model has a complete loss of a gene, this is called a global knockout. This is because scientists have knocked out, or removed, the gene from all cells. When genes are removed from certain cells or removed at a certain time of development, these are referred to as conditional knock out models or cKO.

These tools allow scientists to investigate the precise role of a gene in different cell types or at different times of the mouse’s development. For example, we know that SLC13A5 is found in the brain and also the liver. With the genetic tools available, scientists can remove SLC13A5 from either the brain or the liver, and determine which one, or both, cause issues found in people with SLC13A5 Epilepsy.

Some of the challenges of using mouse models are:

  • Mice are much slower to grow than other models, such as flies, worms, or zebrafish
  • They also produce an average of ~8 offspring per mating
  • They develop in utero, limiting the ability to observe cells growing during early development

Sometimes scientists use rats as another rodent model because they have more complex behaviors than mice and share even more similarities to humans than mice. However, there are fewer research tools available for rat models.

What models are used to study SLC13A5 Epilepsy?

Let’s take the gene responsible for SLC13A5 Epilepsy as an example. There are multiple animal models available to learn about SLC13A5 Epilepsy. Scientists can study this disease by looking at mice that completely lack the SLC13A5 gene. In a scientific paper, if the gene that was removed was SLC13A5, this may be written as SLC13A5-/- or SLC13A5 KO. Scientists have also developed tools to remove genes from specific cell types. For example, scientists could remove SLC13A5 only from brain cells but leave it intact elsewhere. In a scientific paper, this may be written at SLC13A5cKO. For SLC13A5, there is both a global knockout and a conditional knockout (cKO) that is used to study SLC13A5 Epilepsy.

Currently, there are flies that lack the SLC13A5 gene, a zebrafish model in development, and there is also a mouse model that completely lacks the SLC13A5 gene. These models are extremely helpful to improve our understanding of the role of SLC13A5 in the body and SLC13A5 Epilepsy. TESS Research Foundation is also working with scientists who are building additional models, so check back soon!

Which model should you use?

There are many different organism models used to address scientific questions, each with their own strengths and weaknesses. Sometimes the best model to use is a fruit fly, sometimes a worm, zebrafish, or a mouse. There are also other models used that we weren’t able to discuss here. The best model to use depends on the scientific question that is asked and each model adds valuable insight to research. The most innovative science comes about by using each model to answer a different question and pooling all of the information together. Scientists keep making great discoveries using all of these different models.

This article was written by Tanya Brown, PhD. Thanks to Emily Hsu for her editing on all the Science Simplified blogs!

We want to hear from you! If you want to add to our list of topics for Science Simplified, please email Tanya Brown, PhD: [email protected].