January 23, 2021

I, Science

The science magazine of Imperial College

Anita Ramanathan takes a look at how and why mice ended up in our laboratories.

At a conference entrance, a scientist walks around a long, serpentine queue and reaches the check-in counter, only to find the organiser walk away from the table. She lowers her poster board and smirks to her colleagues, “I passed the maze test, and don’t even get a reward?” Even in an ordinary situation, she makes a reference to the laboratory mouse.

Not too many post codes away, a girl sees a flash of fur dash from the balcony to the kitchen and shrieks. She complains to her landlord, “I saw a mouse – again! Why can’t you get rid of these filthy creatures?” she yells, frustrated. “I’m sick of them!”

Depending on who you are, a mouse can be your friend or foe.

The mice that are used in science, we breed and cite; the ones that encroach into our space, we chase out of sight. These members of the Mus musculus species live among us, but thrive in two separate worlds: as the laboratory mouse, an academic marvel; and as the wild mouse, a residential nuisance. At this very moment, as a mouse scurries up a pipe hoping to enter a home and spot food, elsewhere its laboratory counterpart basks in the fortune of an all-you-can-eat feast. Fate and a series of historic events determined the disparity in their lives.

Mice in the wild live in close association with humans in a type of relationship that benefits only them, making them “human commensals”. In fact, house mice have been around humans, based on zooarcheological evidence, for around 12,000 years, since the surge of agriculture during the Neolithic Revolution. As humans in the east Mediterranean began cultivating crops, house mice began to exploit the grain being stored.

So how did the mice migrate from the Eastern Mediterranean to the Americas? Using genetic ancestry analyses based on mitochondrial DNA tests, scientists have been able to trace their path. About 3,000 years ago, during the Iron Age, the house mice migrated westwards of the Mediterranean to north-west Europe. Once on western European soil, the house mice tailgated the British, Dutch and French sailors in their adventures. As the sailors travelled the world and came across new countries to settle in, the mice tagged along with them in their cargoes. Finally, a few hundred years ago, the house mice arrived into America. These mice would soon revolutionize the foundation of genetics, but they didn’t know it yet.

photo of mouse

The mighty Mus musculus house mouse travel great distances with their humans.

Humans soon began to capitalize on their rodent companions. During the 19th century several fanciers in Europe, the United States, and Japan began breeding and trading mice for their unique coat colours, ranging from pure white to jet-black and different shades of brown. The father of modern genetics, Gregor Mendel, is believed to have started heredity experiments using mice in order to study their inheritance of coat colours. But being a religious leader in St. Thomas’ Abbey, Mendel was asked to stop breeding smelly creatures that had sex inside the monastery. With an ability to copulate all year long, a gestation period of only around 3 weeks, and the capacity to produce 4-9 pups per litter, can you blame them? Mendel, overcome by pressure from his bishop, switched to peas as his genetic model. Mendel’s theories of inheriting parental genes, however, did not gain momentum until decades later.

In the 20th century, Mendel’s laws were rediscovered and the race to develop a new genetic model was on. A scientist named Lucien Cuenot decided to finally use mice to demonstrate Mendel’s laws and published the findings of mouse heredity between 1902 and 1905, marking the birth of mouse genetics. Another scientist, Clarence C. Little, also followed suit and became a loyal customer of the mouse fanciers. These researchers quickly began to identify the advantages of using house mice as lab companions: their small size, easy diet, fast breeding and most importantly, their well-studied gene inheritance.

To achieve reproducible results for experiments, researchers in the 1900s began inbreeding the laboratory mice. Inbred mice, produced after 20 generations of brother-sister or parent-offspring mating, are genetically identical to one another. The homogeneity of these mice served as a useful tool for studying the complexities of genetics. In 1909, Clarence C. Little developed the first inbred strain, named DBA, a popular mouse line that is still in circulation. By 1929, he founded the Jackson Laboratory, which is the largest provider of inbred mice in the USA today. With their newly upgraded status, the mice had ultimately found a place of safety and abundance. The hustle was over.

photo of mouse

A mouse from the DBA strain

Being a laboratory mouse means no more stealing food or braving nasty weathers. Life in the mouse vivarium, their new home, is phenomenal! Water and meals are served ad libitum. The nutritional value of the food is tightly controlled and monitored to the second decimal place. The vivarium is maintained at a cozy temperature and the lights promptly go off at a scheduled time. The interiors are so hygienic that any human entering the vivarium has to deck up in protective scrubs and wear shoe covers, a face mask and gloves. All this, not just to protect themselves but to also safeguard the health of the lab mice, as they are liable to pick up infections from us humans. Yes, you read it right. In the field of science, the mice are protected from human infections.

person looking at mouseHumans wear protective clothing around laboratory mice.

Meanwhile, house mice that weren’t destined for academia have spread far and wide, and are ubiquitous in almost every city. They remain a real estate nightmare, and every council’s concern. In fact, their freeloading and bedraggled lifestyle has triggered another field of science, this time dedicated to studying and preventing the spread of rodent-related diseases. However, these sneaky critters continue to dodge mouse traps, evade poison baits and take tips from Jerry as they escape the Toms and predators around them. Their hustle continues.

The laboratory mice and their estranged wild relatives never cross paths. But every time a scientist publishes a finding on mouse behaviour – like freezing in fear, compulsive burrowing of dirt, or self-grooming – one can declare with confidence: You can take a mouse out of the wild, but you cannot take the wild out of a mouse.

Anita Ramanathan (@anitarrn) is a researcher, science writer and storyteller. She is also an editor at the neuroscience education website, Knowing Neurons.

Image 1. Phifer-Rixey and Nachman, Elife, Apr 2015
Image 2. Jackson Laboratories
Image 3. JAX Blogs