zebrafish
斑馬魚
zebrafish (斑馬魚)
斑馬魚 (zebrafish)
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Zebrafish Make a Splash in FDA Research
Source (資訊來源):
Info cited on 2018-06-11-WD1 (資訊引用於 中華民國107年6月11日) by 湯偉晉 (WeiJin Tang)
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Zebrafish Make a Splash in FDA Research
Zebrafish Embryos 350x573
A tiny fish no wider than your thumbnail may someday make a big difference to your health, but not because it's going to show up on your dinner plate.
Zebrafish—so named for the speckled "stripes" along its side and originally found in the Ganges River in East India and Burma—have been making a splash in the world of scientific research for some time. In 2003, the National Institutes of Health (NIH) ranked the torpedo-shaped fish the third most important experimental organism after rats and mice, and it's quickly gaining ground.
At the Food and Drug Administration's (FDA's) National Center for Toxicological Research (NCTR) in Arkansas, scientists are using the embryos and larvae (up to five- to six-days old) of these small, transparent fish to practice what is called, "predictive toxicology."
According to FDA research biologist Jyotshna Kanungo, Ph.D., "Using the embryos of zebrafish as models, we study how various drugs and chemicals affect the organs and systems. We try to get the best possible picture of the hazard that would be involved in taking a drug before it is tested in human patients."
In 2009, Kanungo set up the zebrafish laboratory at NCTR. "Zebrafish make terrific preclinical trial subjects, she says. "They are similar to humans in many ways and have a number of advantages over the other animals used in experimental research, such as laboratory mice and rats because of their fast development and low cost of maintenance."
A Lot Like Us
What makes this little fish such a great scientific subject?
Surrounded by 288 fish tanks in her lab at NCTR, Kanungo notes that unlike the fruit flies and the nematode worm, other popular species studied in laboratories, zebrafish are vertebrates (have a backbone), as are humans. Most of their genes—more than 80 percent—have a human counterpart, she says.
"Because the fish share so many common biological pathways with humans, they make excellent test subjects," says Merle Paule, Ph.D., director of NCTR's Division of Neurotoxicology. (Biological pathways, a series of actions among molecules in a cell, are important to how a body functions.)
The similarities don't stop there. For example, the hearts of zebrafish and humans both have chambers and rhythmically pump oxygen-carrying blood through the body. The eyes of a zebrafish have a retinal structure much like those in people. The tiny fish also have a liver, pancreas, kidneys and intestines.
And you can see right through them.
"It's very exciting, because under a microscope you can watch as their organs and systems develop," Kanungo says. "You can actually see the blood flowing and the heart beating."
Their embryos and eggs — which are fertilized externally and develop outside of the mother's body—are available year-round. "We can watch as the cells of the embryo divide and form different parts of the larvae's body," Kanungo notes. In the span of only two to four days, cells make the eyes, the heart, the liver, the stomach and other functional organs.
Plus, the fish are small, no longer than two or three centimeters, and lay their eggs in large quantities. "In our lab at NCTR, we have the capacity to house about 6,000 of them," Kanungo notes. Introducing drugs or chemicals to the fish is just a matter of putting these compounds into the water. The fish absorb them through their skin.
There is also a cost-savings benefit, as zebrafish are much less expensive to maintain.
"We can treat embryos in the hundreds, even thousands at a fraction of the cost previously incurred," Kanungo says.
In the Lab: NCTR Studies
Being able to maintain so many fish at one time also helps NCTR researchers rapidly conduct large numbers of chemical, genetic or pharmaceutical tests. "We can test 20 different concentrations of a drug or chemical in just ten minutes," Kanungo notes, and screen as many as 384 embryos within the same time period.
Today, NCTR is using the zebrafish in a number of different studies.
Scientists are studying the effects of ketamine (a pediatric anesthetic regulated by FDA) on the overall development of embryos as well as on the cardiovascular and nervous systems.
Using transgenic (genetically-altered) zebrafish embryos, scientists are investigating the effect of copper nanoparticles—frequently used in medical devices, paints and fabrics—on biological systems.
Zebrafish have neuromasts (small sensory patches) similar to those lining the inner ear of humans. Using dyes, scientists can stain the neuromasts to make them more visible and monitor the effects of compounds such as nicotine, ketamine, and ethanol on hearing.
Using zebrafish, scientists have shown that both ketamine and nicotine act as endocrine disruptors that interfere with normal hormonal levels.
Dr. Paule explains that zebrafish do have distinct differences from both humans and other laboratory animals, including a different metabolism and a far less complex nervous system. Nonetheless, he calls the fish a "gatekeeper," and says, "If we introduce a drug/chemical to zebrafish and there's a negative effect, it's a red flag, and it alerts us to take a closer look for toxicity if subsequent studies are warranted."
April 8, 2013
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2018-06-11
為什麼選用斑馬魚動物模式
Source (資訊來源):
Info cited on 2018-06-11-WD1 (資訊引用於 中華民國107年6月11日) by 湯偉晉 (WeiJin Tang)
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為什麼選用斑馬魚動物模式
斑馬魚(ZebraFish)是特別易於使用於遺傳學及脊椎動物發育研究的一種生物。斑馬魚的許多組織和器官,包括心臟,骨骼,胰腺,腎臟等都與人類和其他高等哺乳動物類似。斑馬魚胚胎在發育過程中,特別適合各種物理、化學和遺傳工程操縱。使用基因轉殖斑馬魚作為藥物測試,環境污染物的測試有顯著的優點。飼養容易、繁殖力強,基因已完全解碼,是最新的脊椎動物研究模式。
斑馬魚胚胎發育機制與哺乳類動物相似,其胚胎大而透明,數量多,方便操作及觀察,廣受發育生物學家喜愛。斑馬魚動物模式對許多其他人類疾病正在開發中,包括神經系統,造血,免疫代謝系統。如轉基因和基因敲除也可用於斑馬魚,並提昇新藥發現及研究。目前轉基因斑馬魚對於特定人類疾病,可以作為藥物篩選模型。斑馬魚提供了一個很好的研究工具。此模式生物將成為一個越來越重要的藥物篩選的工具。其基因與人類同源性相當高,已有多種模仿人類疾病之模型,且水生的特性便於直接投藥,達到突變或治療等目的,在癌症生物學、遺傳學、毒理學、新藥開發等領域皆受歡迎,在台灣也有越來越多斑馬魚實驗室成立及跨領域實驗室投入研究。
早在2013年,美國FDA已證實斑馬魚在毒理研究、臨床試驗於眼睛,心臟,肝臟,胃和其他器官的研究,所以利用斑馬魚來研究可以說是一個非常好的動物模式。
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