I see right through your fishy business!
“Heart on your sleeves!”
“Thin-skinned!”
“Plain as the nose on your face!”
These are among the jeers I am sure one type of fish hears at fish school. I am not talking about some newly discovered species, but a modified version of a very familiar one, the zebrafish.
Zebrafish are invaluable to medicine as they allow scientists to study the biology of human disorders without further harm to patients1. Researchers have used zebrafish since the 1970s to understand a wide variety of topics related to human health, including diabetes and cancer. Zebrafish are used to study how a change in DNA, called a genetic modification, can affect various diseases. These modifications can include the addition or removal of some DNA, often called a gene, relevant to a disease to better understand that DNA’s role in the body and its importance to the diseases.
Fascinatingly – despite drinking their own pee water – zebrafish are surprisingly similar to humans. Their internal organs, blood vessels, and nervous systems are laid out similarly to ours. Zebrafish even produce the same hormones as us, including insulin–a hormone important to diabetes [1,2]. This allows researchers to use zebrafish to better understand how the loss of insulin results in diabetes and how it affects all of the organs in the body.
One major benefit of the zebrafish as a research animal is their small size: adults are no more than 2.5 inches. Researchers can easily observe the effects of a modification over the whole body, rather than just parts of the body like in a larger animal [3]. Zebrafish also have a lifespan of 5 years, which is relatively long for organisms of their size. Scientists can therefore watch how the effect of a modification develops as an individual ages from an embryo to an aging adult3.
While zebrafish skin is clear, the pigment cells that give them their color can interfere with microscopes and cameras scientist use to observe the organs of living fish. Zebrafish skin contains three different pigment-producing cells: ‘dark melanophores’, which are the cells that produce the melanin pigment responsible for the variation in human skin tone; ‘iridophores’, which give fish that iridescent shine; and ‘xanthophores’, which is the yellow pigment particularly noticeable in male zebrafish. Because these pigment cells are literally in the way of the organs researchers are interested in studying, the fish must be euthanized and these organs must be dissected out to be studied.
To overcome this, The Zon lab group in Boston, Massachusetts modified Zebrafish genes to eliminate each of these pigment cells, creating the Casper fish. Much like the ghost they are named after, Casper fish are completely see-through [4]! All their internal organs can be seen without any additional internal imaging techniques or dissections. That means happy researchers who get to monitor the treatment response of an individual’s organs for longer, and happy fish that get to swim another day.
The Zon lab also demonstrated the benefits of their new Casper fish with two experiments. First, they injected fluorescent bone marrow cells into the normal pigmented zebrafish and into Casper fish. While both fish successfully accepted the bone marrow transplant, the fluorescent bone marrow cells could only be seen in the see-through Casper fish. Next, they implanted a tumor into pigmented zebrafish and Casper fish and monitored its growth in each. As expected, the Casper fish gave the best view of the tumor as it grew and its progress could be observed with the naked eye more easily than in the regular zebrafish.
The sky is the limit for how researchers can make use of these amazing Casper fish. And because of the ability to observe the internal organs of these zebrafish without dissections, fewer fish need to be sacrificed, making zebrafish research more ethical and less wasteful.
Sam Fernandes is a part-time biology grad student and a full-time cowgirl. She works in the Rasmussen lab at UW, studying how our biggest organ, the skin, protects us from the elements and lets us feel our world. Sam’s work focuses on how some organisms harness the awesome power of regeneration to give their skin cells unlimited Heath Power (HP). She hopes this work can help those experiencing nerve damage and restore their sense of touch.