Have you ever wondered why do we choose mice over all the other animals to conduct our experiments from testing new drugs to today's COVID vaccine trials? In fact, 95 percent of all lab animals are mice and rats, according to the Foundation for Biomedical Research (FBR)
First Experiment:
In 1909, scientist Clarence Cook Little mated closely related mice for several generations, creating the first inbred strain.
Inbred mice are perfect for the study of the biological effects of genetic mutations or environmental factors such as diet, as the animals are almost like a blank canvas to work from.
Why Mice and Rats?
1.Anatomic, Physiological and Genetic Similarity:
Mice, rats and humans, each have 30,000 genes and of them 95% of the genes are shared by all three species.[1]
This is what makes mice and rats ideal for biomedical research and comparative medicine studies. There is another added advantage, i.e., the wealth of genetic information related to mice and rats that are abundantly available. The human genome was sequenced in 2001, followed by mice and rats in 2002 and 2004 respectively. This implies that complete nucleotide sequences are available of the three species, which would help in comparative studies.[2]
2. Mice are -
Small in size
Cost less to maintain
Can be bred purposely to specific mates in order to generate pure breeds.
The mouse has a short lifespan (one mouse year equals about 30 human years) which means scientists can easily measure the effects of aging.[3]
As the life span is short, several generations can be observed at once.
Adapts well to new surroundings.
They can be grown in a controlled, pathogen-free environment, the effect of environmental factors can be highly controlled.
3. Tools to manipulate their genomes have been available for four decades, i.e. , it is easy to add and delete a specific gene and study the outcomes to understand its role in our body, the role of that specific gene in causing the disease.
Let's discuss a few diseases where mice and rats played a central role in deciphering the disease.
Hereditary deafness is the most common sensory deficit. This is due to mutations or defects in a number of different genes, i.e., heterogeneity which essentially means that a single genetic disorder being influenced by multiple genetic mutations. So many mice models can be made, with a unique mutated gene in each one of them. It becomes problematic to decide where a disease is completely due to genetic makeup or influenced by the environment. This issue can be solved as mice are inbred to identical strains this will ensure that single-gene mutations are carried and they are raised up in a controlled environment, so the effect of environmental factors can be highly controlled. Deafness in mice can be identified by lack of ear flick, i.e., failure to respond to noise.
Rats are preferred for studying cardiovascular diseases, where their larger size is an advantage, especially for facilitating surgical procedures and other types of testing.
Rats are used for behavioral studies because they are much more social than mice and their behavior better mimics behavior seen in humans. For example, the expansion of a three-base pair sequence in the FMR1 gene is responsible for Fragile X syndrome, the most common cause of inherited intellectual disability in humans. This expansion leads to methylation of the FMR1 gene, which essentially means shutting it down such that the gene is not expressed [2].
However, when the FMR1 gene is knocked out in rats, they become less engaged in social play and emit fewer vocalizations during play sessions. These social impairments more closely parallel social behavior symptoms seen in humans with FMR1 mutations.
The Resource Centers take the burden from the individual investigators of preserving the strains and shipping the animals to other researchers.
Importantly, the Resource Centers use strict quality control measures to ensure that the genetics and clean health status of these models are monitored and maintained at the highest standards.
The harm-benefit ratio
An ethical evaluation process is conducted based on the harm-benefit assessment of the experiment. Researchers have to face a review committee and have to justify why they want to use mice and not some other kind of experimentation like cell cultures etc.,
They have to implement the 3Rs (Replacement, Reduction, Refinement) to minimize the harm to the animals and to ensure that the outcomes are scientifically significant and that the quality of the science is high, in order to maximize benefits to humans and animals.
Mice and rats play an indispensable role in biomedical research.
We all enjoy a better quality of life because of the research that is performed on them. We shall forever be indebted for their everyday sacrifices.
REFERENCES:
1. Genome sequence of the Brown Norway rat yields insights into mammalian evolution.
2.The Mighty Mouse: The Impact of Rodents on Advances in Biomedical Research
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