1. PRESENTED BY Mr. SUMAN MANANDHAR I M.PHARM DATE: 26TH AUG
2014 TRANSGENIC ANIMALS & OTHER GENETICALLY PRONE ANIMALS
2. CONTENTS: HISTORY INTRODUCTION PRODUCTION OF TRANSGENIC
ANIMALS ADVANTAGES DISADVANTAGES DIFFERENT TRANSGENIC ANIMALS
CONCERNS AND CONCLUSION
3. HISTORY The first GMO(Genetically modified organism) was
created in 1973 by Stanley N. Cohen and Herbert Boyer. The first
transgenic animals were mice created by Rudolf Jaenisch in 1974.HE
managed to insert foreign DNA into the early-stage mouse
embryos.
4. In mid-1974, scientists called for and observed a voluntary
moratorium(delay or suspension of an activity or a law) on certain
recombinant DNA experiments. One goal of the moratorium was to
provide time for a conference that would evaluate the state of the
new technology and the risks, if any, associated with it. That
conference concluded that recombinant DNA research should proceed
but under strict guidelines. Cont...
5. DEFINITION: A transgenic animal is one that carries a
foreign gene that has been deliberately inserted into its genome.
Genetic material are altered using techniques in genetics generally
known as recombinant DNA technology.
6. PRODUCTION OF TRANSGENIC ANIMALS THE METHADOLOGY Step 1
Construction of a transgene Transgene is a segment of DNA
containing a gene sequence that has been isolated from one organism
and is introduced into a different organism. Transgene made of 3
parts: Promoter: a regulatory sequence that will determine where
and when the transgene is active Gene to be expressed Termination
sequence: a stop sequence
7. Step 2 Introduction of foreign gene(transgene) into the
animal 1. DNA microinjection 2. Embryonic stem cell-mediated gene
transfer 3. Retrovirus-mediated gene transfer Microinjector
8. A female animal is super ovulated and eggs are collected.
The eggs are fertilized in vitro. The transgene containing solution
is injected into the male pronucleus using a micropipette. Eggs
with the transgenes are kept overnight in an incubator to develop
to a 2 cell stage. The eggs are then implanted into the uterus of a
pseudo - pregnant female (female which has been mated with a
vasectomized male the previous night) i. MICROINJECTION METHOD
9. Transgenic animals can be created by manipulating embryonic
stem cells. ES cells are obtained from the inner cell mass of a
blastocyst. Transgenic stem cells are grown in vitro. Then they are
inserted into a blastocyst and implanted into a hosts uterus to
grow normally. ii. EMBRYONIC STEM CELL METHOD
10. BLASTOCYST MICROINJECTION
11. #To increase the probability of expression, gene transfer
is mediated by means of a carrier or vector, generally a virus.
#Commonly used are Retroviruses because of their ability to infect
host cells. iii. Retrovirus-mediated gene transfer.
12. contd #Offspring derived from this method are chimeric,
(single organism composed of genetically distinct cells.)i.e., not
all cells carry the retrovirus. #Chimeras are then inbred fo r 1 0
to 20 generatio ns until ho mo zygo us transgenic animals are
obtained and the transgene is present in every cell.
13. Step 3: Screening for transgenic positives Transgenic
progenies are screened by PCR(Polymerase chain reaction) to examine
the site of incorporation of the gene Some transgenes may not be
expressed if integrated into a transcriptionally inactive site.
Step 4: Further animal breeding is done to obtain maximal
expression. Heterozygous off springs are mated to form homozygous
strains.
14. Importance: Study gene function. Drug testing. Research
into animal and human disease. Improve livestock animals. Use of
animals as bioreactors. Gene pharming, to produce drug in their
milk (e.g.: insulin, cancer drugs) and urine. Toxicity sensitive
transgenic animals to test chemicals. Spider silk in milk of
goat
15. ADVANTAGES: Increased growth rate Increased disease
resistance Increased muscle mass Increased nutritional quality
Increased food conversion rate Improved wool quality Generate large
quantities of human proteins in eggs, milk, blood or urine
Decreased the number of animals used in such experimentation
16. DISADVANTAGES: Breeding problem Multiple functions Some
leads to mutagenicity and functional disorder Expensive Low
survival rate Difficult procedure
17. Rat Cow Pig Sheep Fish Goat Frog Transgenic animals
produced Brinster's growth hormone mouse
18. Some of transgenic rats: 1. Nude mouse: . A nude mouse is a
laboratory mouse from a strain with a genetic mutation that causes
a deteriorated or absent thymus, resulting in an inhibited immune
system due to a greatly reduced number of T cells. . The phenotype,
or main outward appearance of the mouse is a lack of body hair,
which gives it the "nude" nickname. . Valuable to research because
it can receive many different types of tissue and tumor grafts, as
it mounts no rejection response.
19. It is an animal model of essential (or primary)
hypertension, used to study cardiovascular disease. It is the most
studied model of hypertension measured as number of publications.
The SHR strain was obtained during the 1960s by Okamoto and
colleagues, who started breeding Wistar-Kyoto rats with high blood
pressure. 2.Spontaneously hypertensive rat (SHR)
20. A humanized mouse is a mouse carrying functioning human
genes, cells, tissues, and/or organs. Humanized mice are commonly
used as small animal models in biological and medical research for
human therapeutics. Humanized mouse models represent powerful tools
for studying hematopoiesis, inflammatory disease, viral
host-pathogen interactions, and are helping to accelerate the
development of novel therapies in HIV infection and oncology. 3.
Humanized mouse
21. CONCERNS Safety - have a potential human health impact in
regards to: allergens, transfer of antibiotic resistance markers,
and other unknown effects Potential environmental impact -
Unintended transfer of modified genes through cross- pollination,
unknown effects on other organisms in the environment, and loss of
flora and fauna biodiversity Ethics- Are we tampering with nature
by mixing genes among species? Does this create stress for the
animal?
22. CONCLUSION: The creation of transgenic animals has resulted
in a shift from the use of higher-order species such as dogs to
lower- order species such as mice . It holds great potential in
many fields including agriculture, medicine and industry. With
proper research and careful use the transgenic animals can go a
long way in solving several problems for which science doesnt have
a solution till now.