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Zebrafish is the first genetically modified pet for many people.
The full name of Zebrafish Center is National Zebrafish Resource Center. Simply put, it is a place where zebrafish are specially raised and relevant experimental research is carried out. The most striking thing in the whole center is the rows of blue fish tanks, large and small-this is a special zebra fish feeding system. Each group of systems is independent of each other, and there are 45 "rooms" of different sizes in a single system. The whole system is integrated in circulation and isolation, which is especially suitable for raising small aquatic organisms.

Blue tanks for breeding zebrafish in National Zebrafish Resource Center. Photo: Little Xia Yellow Chicken

Every "room" in the system has a small fish 3~5 cm long, which is the core "resident" in the center-zebra fish.

Disguste them. They are the antidote to human beings.

As a small Cyprinidae fish native to India, zebrafish is much more elegant in color matching than other fish of the same genus, with only a small silver-gray body lined with several gray-blue longitudinal stripes.

Small fish with zebra stripes. Photo: goodfreephotos

Many tourists will ask such a question: these zebrafish are ugly and don't look edible. What are they for?

The so-called expert sees the doorway, and the layman watches the excitement. For life science related fields, these ugly zebrafish are crucial model creatures.

Four commonly used model organisms in life sciences: Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster and Arabidopsis thaliana. Photo: Andre Cabos, July issue of Wikimedia.

The so-called "model organisms" refer to the organisms selected by scientists for scientific research and revealing some common life phenomena, such as peas used by Mendel in high school biology textbooks, fruit flies and house mice observed by Morgan. Are classic model creatures.

"933 1" is the code word for biology students to smile after hearing it. The real yellow circle, green circle, yellow wrinkle and green wrinkle peas are used in the photo, which vividly shows the law of free combination of genes discovered by Mendel. Photo: Calendar Mom

Life science research is inseparable from ideal model organisms, but due to the lack of ideal model animal, the development and genetic research of vertebrates has long lagged behind that of invertebrates.

Although rodents promote the development of modern advanced genetics, their embryos are deeply buried in the mother's uterus, so it is difficult for researchers to observe their development. Although Xenopus laevis is a good material for embryology, it is difficult to become a good object for genetic research because of its slow reproduction.

The classic model organism Xenopus laevis. Image source: Ben RS chr/ Wikimedia

On the other hand, zebrafish has many excellent experimental characteristics, such as easy to obtain, easy to raise in large quantities, high reproductive capacity, in vitro spawning, in vitro fertilization, transparent and easy to observe embryos, simple and repeatable operation, etc., so it has become an ideal experimental object for biologists.

More importantly, zebrafish and human genes are as high as 87% homology-which means that the experimental results on zebrafish can be analogized to humans in most cases. Therefore, a large number of embryology, genetics, toxicology research, as well as various experiments related to human diseases, zebrafish was selected as the model organism.

From the point of embryology and genetics, zebrafish embryos are transparent, which is convenient for observing the development process of various organs and tissues. Moreover, they are more likely to produce haploid offspring, which are very suitable for observing the traits controlled by recessive genes, and can also be rapidly propagated into homozygous individuals of this gene.

Transparent zebrafish embryo. Picture: Adam Amsterdam? et。 Al. ? / ? PLoS biology? (2004)

From the toxicological point of view, using zebrafish to detect the teratogenic effects of various chemicals in the environment has the characteristics of low cost, few influencing factors, good repeatability, simple operation, high sensitivity, and simultaneous observation of multiple toxicity indexes, and can further study the toxicity mechanism of pollutants.

Fetal alcohol syndrome

The researchers treated zebrafish embryos with different concentrations of ethanol, and found that with the increase of ethanol concentration, the teratogenicity and mortality of zebrafish embryos increased, the hatching rate decreased, the embryo length shortened and the heartbeat slowed down.

Among them, developmental malformations are mainly manifested as caudate node, smaller eyes, pericardial edema and spinal curvature, which are similar to the symptoms of human fetal alcohol syndrome. Therefore, the toxic effect of ethanol in human embryonic development has been clarified.

In recent years, it is a hot research topic in the world to establish a disease model by using zebrafish and study the methods to cure human-related diseases. Up to now, thousands of zebrafish mutants have been found, which can simulate human anemia, deafness, retinal degeneration, myasthenia, malignant tumor, Alzheimer's disease and other diseases.

In recent years, people even found that zebrafish can also be used for the study of depression and drug addiction. Moreover, zebrafish is highly sensitive to psychotropic drugs, such as opioid analgesics, antidepressants and anxiolytics, so it can be used as an important tool to study drug metabolism and side effects.

Zebrafish was used in the related research of ketamine (commonly known as K powder) addiction. Photo: US Food and Drug Administration /Flickr

In addition, zebrafish fins, scales and part of the heart, brain and spine can be regenerated, so it is of great significance for the treatment of human amputation.

Zebrafish is not the only experimental fish devoted to life science. In recent years, medaka has gradually become a hot spot in the field of physiological research, and was even sent into space as a representative of vertebrates in 1994. However, the Institute of Aquatic Sciences of Chinese Academy of Sciences independently developed a kind of "poisonous fish" (not a small amount, but a "rare fish") for toxicity test and environmental monitoring. The picture shows rare carp. Photo: Little Xia Yellow Chicken

Genetically modified pets in the laboratory

However, experimental fish is far from everyone's life. For most people, the contact with zebrafish is mostly in the aquarium shop of the big flower and bird market.

Zebrafish is almost a necessary commodity for ornamental fish shops because of its huge output and good skin color. In the "face-looking" ornamental fish world, zebrafish also shows amazing diversity: some zebrafish fins are slender and elegant, and they are called "long-finned zebrafish"; Some zebra fish patterns become intermittent spots, called "leopard zebra fish"; And even the most common zebrafish, the pattern of gluteal fin will be different.

Zebra fish with spots. Image source: bernat Arendis /flickr

However, among many zebrafish, the most prominent one is the recently appeared "color zebrafish". Some of these zebrafish are bright red, some are warm yellow, and some even glow green under purple light.

And you will never think that these colorful zebrafish are actually by-products of the above-mentioned experiments.

Although the zebra fish used in the experiment has outstanding advantages, there is still a problem unsolved-the fish embryo is small and transparent, and the development process is clearly displayed, but careful observation has become a problem.

In order to solve this problem, scientists introduce fluorescent protein into zebrafish fertilized eggs through transgenic technology and express it in specific tissues and organs, so that the development and physiological changes of specific organs can be observed conveniently under fluorescent microscope, and even the whole process of embryo development and the influence of exogenous substances or gene mutations on organ development can be dynamically tracked.

Zebrafish with green fluorescent protein in the heart. Image: NIGHTSEA/YouTube

The fluorescent transgenic zebrafish was invented by China scientists from the National University of Singapore. Transgenic zebrafish can emit green fluorescence, mainly due to a green fluorescent protein (GFP), which was isolated from Victoria jellyfish and can emit green fluorescence under natural light.

Illuminate protein of Life Science.

GFP was first isolated by Shimura Satoshi of Nagoya University in Japan, and he has been working on GFP since then. After GFP was isolated, Professor martin chalfie of Columbia University was keenly aware of its huge application prospect, and creatively transferred GFP gene into nematodes to make them emit green fluorescence.

At the same time, Qian Yongjian, a Chinese-American scientist, transformed the GFP gene and created a brand-new GFP variant, which made it emit stronger and more diverse light, such as blue-green, blue and yellow light, thus making GFP more widely used.

In 2008, these three scientists won the Nobel Prize in chemistry for their research achievements in fluorescent proteins.

The picture shows E.coli transformed by green fluorescent protein. Photo: DanceWithNyanko

Initially, transgenic zebrafish was used to monitor water pollution. Scientists have found that zebrafish can respond to environmental changes in the surrounding waters. Once the content of pollutants or toxins (such as dioxins or PCBs) in the environment increases, these fish will produce some special enzymes, and the enzyme content will increase with the increase of toxins.

Once the transgenic zebrafish is put into water and polluted, the expression of environmentally sensitive enzymes in zebrafish will increase, and correspondingly, the intensity of green fluorescence emitted by the fish will also increase. In this way, we can know the environmental pollution by detecting the fluorescence intensity. These fluorescent zebrafish are also called "ecological alarms".

A large school of fluorescent zebrafish. Image: Ruby Jylin/YouTube

However, due to testing, it is necessary to put genetically modified fish into natural waters, which may cause a series of problems such as genetic pollution. Therefore, the application prospect of fluorescent fish in ecological detection is increasingly dim.

Starting from 200 1, the National University of Singapore cooperated with York City Science and Technology Company of the United States to open up a new market for fluorescent transgenic zebrafish-ornamental fish. After more than two years of extensive environmental risk assessment, on February 9, 2003, 65438, the US Food and Drug Administration decided that as an ornamental fish, transgenic zebrafish Glofish? There is no environmental risk and it will not enter the human food chain, so Glofish is approved? List request.

Purdue University found that wild zebrafish has an advantage in the reproductive competition with red transgenic zebrafish. Although wild female zebrafish will prefer to choose red zebrafish with brighter colors, wild male zebrafish will violently expel red zebrafish, so that almost all red zebrafish will disappear after 15 generations.

Fluorescent fish? It also became the first genetically modified animal to be listed in the United States.

Fluorescent fish? All kinds of fluorescent zebrafish are sold. Photo: glofish.com.

In 2006, researchers used the red fluorescent protein gene from coral (that is, the most common red zebrafish, and the ecological bottle is often regarded as the "persecution object") to cultivate a red fluorescent zebrafish strain; At the same time, an orange-yellow fluorescent zebrafish strain was cultivated by using a series of fluorescent protein genes of jellyfish. 20 1 1, people developed blue fluorescent and purple fluorescent zebrafish strains.

In addition to zebrafish, people are also "hurting" other small fish, such as the fluorescent medaka developed in Taiwan Province Province, China. A steady stream of fluorescent fish of various colors has become the most accessible transgenic animals in our lives.

From the humble freshwater fish, to the star model creatures in the field of life science, to the most common ornamental fish around, zebra fish has created one legend after another with its small body.