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Animals in research: rats

Our series, Animals in Research, profiles the top organisms used for science experimentation. In this instalment, we look at the original lab rats: Rattus norvegicus. Rats have a long history in medical…

From street scourge to lab hero: rats have provided us with significant insights into human diseases and disorders. ressaure

Our series, Animals in Research, profiles the top organisms used for science experimentation. In this instalment, we look at the original lab rats: Rattus norvegicus.

Rats have a long history in medical research: they were the first mammalian species specifically domesticated to be used in the laboratory.

Records dating back to the 1850s show these animals were derived from those bred by rat fanciers who collected them for their unique coat colours and behavioural characteristics.

The success of the rat in research today has been linked to the Wistar Institute in America and their development of the Wistar albino strain. There are currently 117 albino strains of the laboratory rat, all of which can be traced genetically back to the one rat, likely to have arisen as a mutation from a hooded (piebald) rat strain.

A hooded (piebald) rat. Benmitch

Since their development as a laboratory species, rats have been used to answer a wide range of basic science questions ranging from physiology, immunology, pharmacology, toxicology, nutrition, behaviour and learning.

Consequently, a large amount of data has been collected that has translated into their extensive use as a model for human disease.

Rats vs mice

Researchers will choose rats over mice when it comes to their use in research for a number of reasons. They are larger in size which makes handling, sampling and performing procedures easier.

For physiological studies, we know a lot more about the responses and pathways in rats than we do in mice due to the wealth of data collected over years of study in the rat, meaning much of the foundation research is already done.

Some work suggests the rat more accurately reflects human physiology than mice do, mimicking human disease more accurately in many cases.

Behavioural research also shows they are more suited to studies of learning and cognition because they are more capable of learning tasks than mice.

The first rat maze was built 100 or so years ago by experimental psychologist Willard Small, who wanted to study the process of learning, and since then rats have enabled the development of many complex learning and conditioning theories.

Their ability to learn, remember, press buttons, levers, and even ride skateboards gives them a huge advantage over mice and also allows us to look at the most basic principles behind learning and behaviour which can then be translated to our knowledge of human behaviour and learning.

A rat learns to press a lever for water, but only when the light comes on.

The main advantage that mice did have over rats until the past few years was that scientists had the ability to manipulate mouse DNA to produce transgenic animals, where specific genes can be modified or even removed in order to study their function in health and disease.

But with the advent of the mapping of the rat genome and recent technical advances, this can now also be done in rats, allowing the creation of “knock-in” (the insertion of a gene at a specific location on the chromosome) and “knock-out” (making a gene inoperative) rat strains to study very specific research questions.

Biomedical research

Rats have a prevalence within biomedical research second only to humans and they share 90% of the genome with humans. Almost all disease-linked human genes we currently know of have equivalent genes within the rat genome, making them a suitable research tool.

A rat in a radial arm maze - a commonly used memory task.

Well-established strains of rat are used to study a number of human diseases such as:

  • obesity and diabetes
  • cancer
  • cardiovascular disease (including high blood pressure and heart failure)
  • neurological diseases (such as Parkinson’s disease)
  • inflammatory and immune mediated diseases (such as certain types of kidney disease and multiple sclerosis)

A Zucker rat, bred for obesity research. Wikimedia Commons

The strains of rat that have been developed to express human diseases were achieved through a number of different processes. It may be that the strain carrying a particular disease feature occurred spontaneously and the animals were then selectively bred. In some cases this has led to identification of the genetic mutation that causes a comparable human disease.

This is what happened with the PCK rat (a rat with a mutation in the pck gene). Genetic analysis of the mutation in the PCK rat, which had a kidney disease called polycystic kidney disease (PKD), led to the discovery of the PKHD1 gene, which encodes for a protein called fibrocystin.

Researchers went back to the human data and found that a mutation in the same gene was also responsible for PKD in humans.

Alternatively, a genetic defect may be “introduced”. This is what was done recently when a new model of Parkinson’s disease in rats was produced by expressing the mutant human gene for a common genetic cause of Parkinson’s in the brain of Wistar rats.

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In some cases, genetics and environment can interact, and a change in the rats’ environment can induce disease in susceptible animals. High blood pressure is a good example. Sprague Dawley rats were fed a very high salt diet, and the animals were then selected and bred on the basis of their blood pressure either increasing or staying normal.

Within three generations of breeding, salt-sensitive and salt-resistant strains were clearly evident, suggesting for the first time that salt sensitivity was an inherited trait and that similar factors may apply in humans.

These rats are now widely used to study salt and the role it plays in causing high blood pressure in people.

Other models of disease in rats may be induced by chemical or surgical means.

The rat has allowed us to build up an incredible wealth of knowledge about basic biology and complex physiological interactions, and has served as a model of human disease and learning, much of which has been translated to greater knowledge about humans.

While we will never be able to have a model that fully replicates the extent of the our own complex physical and behavioural state, the fancy rat has greatly progressed our understanding of many different diseases and disorders, and they will likely continue to provide a very valuable contribution to research.

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5 Comments sorted by

  1. Rob Buttrose

    University of Melbourne

    Research scientists involved in animal experimentation really do need to stop seeing lab animals as "furry test tubes". http://www.newscientist.com/article/dn16301-dont-treat-animals-as-furry-testtubes.html#.Ujpk5DYSZ8E One wonders how much ethical training they take in their degrees, which I believe in most institutions is mandatory. What’s the bet they are never exposed to the position of many ethicists and philosophers (and an increasing number of medical scientists) that harmful experimentation…

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    1. Miles Ruhl

      Thinker

      In reply to Rob Buttrose

      Hear, hear Rob.

      I was thinking the same thing; not a peep about the ethics of such experiments anywhere in the article.

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    2. Erin Lynch

      Masters Student at Macquarie University

      In reply to Miles Ruhl

      There was no mention of ethics at all in this article because the brief for writing it was to only mention how the rats are used in research, (as part of a series of focus articles) and to not mention ethics as there are other articles on The Conversation that have done this.
      For example:
      https://theconversation.com/the-elusive-ethics-of-animal-ethics-committees-10056
      https://theconversation.com/animals-in-research-benefits-ethics-and-assessment-15467

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    3. John Reynolds

      materials engineer

      In reply to Erin Lynch

      Besides, if the paper by Nobis is any indication of the quality of the ethical literature, knowing that such arguments exist will never help anyone change their views.

      1. It is dry as a board- you REALLY need to be wanting to be convinced to get past the first page or two without falling asleep. (Reading it suddenly made me feel more positive about technical journals in my field)

      2. The argument falls on a heap as soon as you get to premise 3, which is at very best based on a very optimistic interpretation of facts, and at worst silly.

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    4. Rob Buttrose

      University of Melbourne

      In reply to John Reynolds

      From the article;

      Premise 3. The best explanations for why these human experiments are morally wrong support belief that similarly harmful nontherapeutic experimentation on (conscious, sentient) animals is morally wrong also because these humans and animals share morally relevant properties.

      If you were aware of the literature, you would know this claim is not unusual and Nobis does defend it in the body of the article, the key bit being "humans and animals share morally relevant properties".

      In contrast , I see no argument from to support your assertion "The argument falls on a heap as soon as you get to premise 3, which is at very best based on a very optimistic interpretation of facts, and at worst silly." That claim is just noise as you have expressed it.

      If the article is too intellectually taxing for you, I can suggest other presentations of a similar position on animal experimentation which are more approachable.

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