Mutant Mice Are Bred to Order

Some are fat, others tiny. And one is just having a bad hair day

The Obese mouse may look awfully cute, but its condition comes with a litany of health problems. This strain can have diabetic-like symptoms, poor body temperature control, low fertility, impaired wound healing, and pituitary and adrenal abnormalities. Some of these mutants reach three times the weight of a normal mouse. Their obesity is caused by a spontaneous mutation that affects leptin, a protein hormone associated with metabolism, rather than a McDonald's addiction. The obesity mouse is used as a model for a number of human ailments, including diabetes, obesity, endocrine deficiencies and fertility defects. Brooke Borel

Head Tilt Mouse

Ever since Mario Capecchi, Martin Evans, and Oliver Smithies created the first knockout mouse in 1989, genetically engineered animals have steadily increased in popularity for all kinds of biology research: simply pick a gene, turn it off in the mouse, and see what happens.

Knockout mice are undoubtedly helpful animal models for many human genetic disorders. But there is still plenty of potential for discovery in mice that go through spontaneous mutations: indeed, these natural mutations can have high levels of complexity and diversity, leading to surprising phenotypes that give insight to human genetic disorders. Last week in at Jackson Laboratory‘s 50th annual Short Course in Medical and Experimental Mammalian Genetics in Bar Harbor, Maine, Popular Science got a peek at 150 of the Lab’s 10,000-plus mutant mouse strains.

See the photo gallery

Jackson Lab has one of the largest populations of spontaneous mutant mice in the world: out of the 10,000 or so total strains, over 500 came from natural mutations. The lab also has around 1,500 targeted strains, knockout mice that which were genetically engineered, and various flavors of regular, healthy mice.

Shiverer Mouse

For over 20 years, researchers here have conducted “deviant searches” at the lab, which help link specific genetic mutants to an appropriate area of research. Every two weeks, mice that differ physically or behaviorally from their littermates — usually anywhere from five to a few dozen — are pooled together. Jackson scientists look for mice that exhibit phenotypes (the observable characteristics of their genotypes) that are common to whatever disease or disorder they are studying, and take those mice back to their lab. This process has led to the discovery of hundreds of genes associated with genetic diseases or disorders. Some classic examples include diabetes and obesity mouse models, which led to modern-day metabolism research.

The characteristics of some strains are hard to detect in a photograph or video, like the Social Anxiety mouse, which hangs back from its brothers and sisters and has a hard time getting a date (poor things are often too afraid of contact to mate). But others have obvious physical or behavioral traits, like those in our gallery.