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Zebra
Fish as a Scientific Tool for Study of Genetics and Developmental
Biology in Vertebrates
Sallie
Boggs, PhD
Finformation,
July
2002
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This
article is the first in a new series. In some ways it is a continuation
of my previous series entitled “Aquarium Critters in Science.”
I have used, and will continue to use, Science Magazine as
my primary source of material and zebra fish are frequent subjects
of articles in that magazine. That was not always the case. I remember
the beginning of the so-called “zebrafish era.” The late
George Streisinger is called the “founding father” of
what is now called “zebrafish research.” In 1981 he published
a method to use zebra fish (then called Brachydanio rerio) to screen
for mutants among parthenogenic (I will explain this later) offspring
of mutigenized females (1).
Previously Dr. Streisinger had made major contributions to deciphering
the genetic code of T4-phage (a virus that infects bacteria). Dr.
Streisinger dreamed of using the power of the molecular techniques
and principles used with T4-phage to study the genetics and development
of a vertebrate. As a fish hobbyist who knew how easy it was to raise
and maintain zebra fish, he began studying them as a potential model
system. As it turned out, Their special characteristics make zebra
fish an ideal model system. Zebra fish are small enough to keep in
the large numbers required for genetic studies, but large enough to
do classical embryological manipulations such as transplantations.
They have a short generation time of about 3 months, fertilization
is external and therefore controllable, embryonic development is rapid
and the embryos are clear.
In spite of the obvious qualities, there were many details to work
out. It took almost ten years before Dr. Streisinger’s group
was ready to publish their first paper using zebra fish. This paper
(1) proved to be a landmark. During this period he described the normal
morphological and functional development of the zebra fish egg and
embryo and developed genetic and husbandry techniques.
A friend of his, Roger Hawthorne of the Albany Aquarium said, “George
Streisinger was adamant about obtaining pure strains of zebra fish.
The first ones that he purchased for his research, his "A"
strain, ---- were collected from the wild in India--- were a very
large, well-colored fish that were nearly 50% larger than the standard
zebra fish in the trade. They had better color, larger finnage and
were marked with more yellow, even in the females. Their fins were
less pointed and more rounded. The body had an overall blue cast.
These fish pleased George immensely.” He also obtained a so-called
'Albino' strain that turned out to be only a 'golden' variety of small,
anemic fishes.
Dr Hawthorn said, “I feel that the possibility of obtaining
the Albinos was the deciding factor in choosing the zebra fish as
his research model. I had recommended the Tans Mountain Fish (Whitecloud),
as it was so similar to the zebrafish but could hatch well and grow
at 60 - 85° F. Heated rooms were not necessary. But, the 'Meteoer'
(longfin) Whitecloud was behind the Iron Curtain and was, at that
time, impossible to obtain.”
When I read Streisinger’s classical paper in Nature,
reporting the first successful cloning of a vertebrate in the laboratory
(1), I was so excited that I called George and asked if I could come
to his lab for two weeks to learn his techniques. He was very gracious,
even though I explained that I probably could not use fish for my
research. Possibly he was just being kind to a fellow fish lover.
We chose a time for me to go to his lab in Eugene Oregon and when
he found out that I was paying my own way, he arranged housing for
me at his expense. Everyone in his lab was extremely open and helpful.
I saw their fish hatchery and nursery. They made their own food and
distilled water and reconstituted it to their own specifications.
They really did have huge very healthy looking fish. They even arranged
their experiments so that I was able to witness each maneuver in the
complex process that would normally require over 4 months. It would
have taken at least a one year sabbatical to really learn the system,
but it is an experience I will never forget.
Soon the model caught the interest of geneticists and developmental
biologist, and now rivals the popular Drosophila (fruit fly)
and worm models, I have secretly felt pride to have been one of the
first to realize that this was a great breakthrough destined to change
research.
In future months I will give more specifics about the methods and
discoveries, but here I will give some examples of why scientists
are so happy with this model. In spite of the distance between man
and fish, a remarkable number of zebrafish (the scientists merge the
two words) genes are homologous (almost identical) to human genes.
This means the genes are very basic “old” genes. For example,
Nancy Hopkins, a biologist at the Massachusetts Institute of Technology
(MIT) has found that a gene required for the zebrafish to grow a liver
and gut is 80% identical to a human gene. Before the zebrafish experiment,
scientists did not know what the human version of the gene did, but
there is a mutation in the zebrafish that explains it.
In future articles I will go into more details about the genetic studies,
physiology and discoveries made through zebrafish. I will also tell
you how to clone zebrafish. Meanwhile, if you can’t wait see
the seminal paper and look at the technical book listed below.
1. Streisinger, G., Walker, C., Dower, N., Knauber, D. and Singer,
F. 1981. Production of clones of homozygous diploid fish (Brachydanio
rerio). Nature 291: 293-296.
2. http//:www.zfish.uoregon.edu/zf_info/zfbook/zfbk.html
The Zebrafish Book: A guide for the laboratory use of zebrafish
Danio rerio. |
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