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Animal Biotechnology

Dogs have been selectively bred for thousands


of years, sometimes by inbreeding dogs from
the same ancestral lines, sometimes by mixing
dogs from very different lines
The same process for horses, cows, cats, etc

Dogs breeds

Horse breeds

Cats breeds

Objective
Use of biotechnology to improve animal health,
productivity and reproduction
Animals provide a number of products we use in
every day life:
Milk
Leather
Wool
Eggs
Meat

Improving Animal Health


Improved Diagnostic testing
Monoclonal antibodies
Pregnancy testing
Brucellosis

Treatment for disease


Caused by viruses and bacteria

Genetically engineered vaccines


Not live disease causing agents

Healthier Livestock
Scientists are trying to find genes that cause or resist
certain diseases of livestock, such as "mad cow
disease.
Once these genes are found in livestock, scientists
can breed livestock for the resistant gene and
develop vaccines and diagnostic tests to prevent
these diseases.

Animal Disease Diagnosis


ELISA tests
Utilize antigens to determine the presence of
antibodies for a given pathogen in a blood sample
Antibodies indicate the presence of a particular
pathogen being fought
The tests are usually produced from antigens
extracted from research animals

Animal Disease Diagnosis


Bacterial Infections
Are tested in animals by biotechnology by
culturing samples in an incubator
Different agar medias can be used to determine
the presence of different bacteria upon
examination after growth

Animal Disease Prevention and Treatment


Biotechnology has enabled researchers to
produce animals with genetic resistance to
many pathogens
Use gene segments from naturally resistant
organisms
Find the gene in sharks that makes them resistant to
cancer for use in humans
Produce animals with gene segments coding for the
production of proteins to attack potential parasitic
organisms

Animal Disease Prevention and Treatment


The production of antibodies in one organism
for use in another is an important
biotechnology technique used in vaccines
Jumpstarts the immune system of an animal
Also used in humans

Animal Disease Prevention and Treatment


The utilization of genes coding for the
production of certain medical compounds
(including antibiotics) in a variety of livestock
enables agriculturalists to
Provide preventative medication in semicontrolled doses to populations on a large scale

Improving Productivity
Transgenic
Animals that have been genetically engineered
DNA has been shared between organisms
Gene transfer

Can be used to produce medicines for humans

Function of Animal Hormones


Anabolic Steroids
Specialized hormones that are partially responsible
for muscle growth and development
Even with prolonged use, steroid use in animals has
little effect on muscle and bone
USDA and FDA have approved the use of low levels
of hormones in beef cattle, dairy cattle, and hogs
HORMONE USE IN POULTRY IS STRICTLY
PROHIBITED

Improving Productivity
Somatotrophins
Hormones produced by the pituitary gland
Circulates in the blood
Directs growth and fat deposits
Regulates milk production in females

Somatotrophins
Examples:
bST
Bovine somatotrophin
Increases weight
Leaner meat

1944: 25.6 million animals; total annual milk production of 53.1 billion kg. 1997: 9.2
million animals; total annual milk production of 84.2 billion kg.

About half of this 369% increase in production efficiency is attributable


to genetic improvement enabled by AI

A
I

VandeHaar, M.J. and St-Pierre, N. (2006). Major Advances in Nutrition: Relevance to the Sustainability of the Dairy
Industry. Journal of Dairy Science 89, 1280-1291.
Van Eenennaam NIAA 4/16/2013

Average annual milk yield and carbon footprint per kg


milk - across global regions. Data adapted from FAO.
,

Van Eenennaam NIAA 4/16/2013

Sites working on GE livestock for food 1985


North America, Europe and Australasia

Van Eenennaam NIAA 4/16/2013

Sites working on GE livestock for food - 2012


Asia and South America are moving forward
with this technology in their animal agriculture

Van Eenennaam NIAA 4/16/2013

Somatotrophins
pST
Porcine somatotrophin
Increases feed efficiency
Reduces fat

Improving Reproduction
Embryo Transfer
Performing a superovulation of a female
Fertilizing the eggs
Removing the fertilized embryos
Placing live embryos in other animals (of the same
species)

Biotechnology Techniques in Animal Breeding


Artificial Insemination
Process of extracting and diluting semen from a
male animal for use in a female animal
Allows for outstanding genetic characteristics to
be spread through a population rapidly with
minimal expense and high success
One ejaculate can produce more than 60 semen straws
in cattle and horses

Biotechnology Techniques in Animal Breeding


In Vitro Fertilization
A more common method is transferring fertilized
eggs from a super-ovulated female to other
females
One female can produce many times more offspring

Improving Reproduction
Cloning
Makes animals have identical genetics
Embryo splitting
Nuclear transfer

Most rapidly increases uniformity in a


particular species of animal

WHY CLONE ANIMALS?


The possibility of cloning a valued pet
provides its owner with a degree of hope.
Cloning could provide blind persons with more
of the very best sight dogs.
United Kingdom Dairy producers are cloning
elite dairy cows and bulls to increase the
supply of superior genetics. Horse breeders
may want to propagate their horses' athletic
and genetic qualities.

Cloning History
First animal cloned was a tadpole in 1957
First animal cloned from diploid cells was
Dolly the sheep in 1996
In 2002, a private company claimed to have
successfully cloned the first human child

Mammal Cloning Timeline


1984 A live lamb was cloned from sheep
embryo cells

Megan and Morag

1986 Early embryo cells were used to clone


a cow
1993 Calves were produced by transfer of
nuclei from cultured embryonic cells
1995 Two sheep, named Megan & Morag,
were cloned using embryo cells

Dolly

1996 Birth of Dolly, the first organism to be


cloned from a fully differentiated adult cell
1997 Transgenic sheep named Polly was
cloned containing a human gene
http://www.cnn.com/2001
/WORLD/europe/08/06/clo
ne.critics/index.html

1998 50 mice were cloned in three


generations from a single mouse
1998 8 calves were cloned from a single
adult cow, but only 4 survived to their first
birthday
1999 A female rhesus monkey named Tetra
was cloned by splitting early embryo cells.
2000 Pigs and goats reported cloned from
adult cells
2002 Rabbits and a kitten reported cloned
from adult cells

http://hs.houstonisd.org/
hspva/academic/Science/
Thinkquest/gail/text/bene
fits.html

Cloning
A genetically identical
copy of a cell or whole
organism

Cloning
Embryogenesis the process by which the
embryo forms and develops
Zygote fertilized egg
Blastocyst early stage embryo prior to
implantation

Cloning Methods
Embryo Twinning

Embryo Twinning Animation

Cloning Methods
Somatic Cell Nuclear Transfer

Somatic Cell Nuclear Transfer

Source: Advanced Cell Technologies

Cloning Methods

A look at Dolly the Sheep

Cloning Methods
Somatic Cell Nuclear Transfer

SCNT Animation

Cloning Methods

Click and Clone a Mouse

Limits to Cloning
Decrease Genetic Diversity

Limits to Cloning
Epigenetic Effects

Limits to Cloning
Efficiency and Cost Effectiveness

Comparison of Cloning Success


Rates in Various Animals
Species

Number of
oocytes used

Number of
live offspring

Notes

Mouse

2468

31 (1.3%)

Bovine

440

6 (1.4%)

2 died

Sheep

417

14 (3.4%)

11 died
within 6
months

Pig

977

5 (0.5%)

Goat

285

3 (1.1%)

The table shows success rates of cloning when mature mammal cells were
used.

Yanagimachi, R. 2002. "Cloning: experience from the mouse and other animals." Molecular and Cellular Endocrinology. 21 March,
187.

Clone Birth Defects


Cloned offspring often suffer from large offspring syndrome,
where the clone and the placenta that nourished it are
unusually large.
Cloned offspring often have serious inexplicable respiratory or
circulatory problems, which causes them to die soon after birth.
Clones tend to have weakened immune systems and
sometimes suffer from total immune system failure.
Very few clones actually survive to adulthood.
Clones appear to age faster than normal.
Clones experience problems associated with old age, such as arthritis, while
they are still young.
This may be due to the fact that clones have shorter telomeres

Limits to Cloning
Abnormal Development

Limits to Cloning
Premature Aging

Telomerase Animation

The Future of Cloning


Increase in genetic gain

The Future of Cloning


Consistent Quality

Clones and Cloning

Dolly, First Mammal Cloned From an Adult Cell

Dolly as a lamb with


her surrogate mother

Dolly, as an adult

http://www.harlemlive.org/community/health-science/scientificcommunity/index2.html

Dolly with her surrogate mother

Dolly
Born in July 1996 at the Roslin
Institute in Scotland.

Dolly with her first


newborn, Bonnie

First mammal to be cloned from an


adult mammal using the nuclear
transfer technique
277 attempts were made before the
experiment was successful
Dolly died in February 14, 2003 of
progressive lung disease at the age
of 6; whereas normal sheep can live
up to 12 years of age.

Cloned kitty

The first two cats cloned by chromatin transfer

Cat Clone

Donor

Surrogate mother with clone (CC)

Out of 87 implants only CC survived to birth

Donor & Clone

Rainbow & CC

http://www.usatoday.com/news/science/2003-01-21-cloned-cats_x.htm

PERPETUATE, a
privately held
company, was
founded in 1998
by Dr. Heather
Bessoff and Ron
Gillespie
Lucky United Kingdom

Human Clone
Britain grants embryo cloning patent
and became the first country in the
world to grant a patent covering
cloned early-stage human embryos.
The decision ignited new controversy
among biotechnology critics even
though the Geron Corporation, the
company licensed to use the patent,
has no intention of creating
cloned humans.

The Next Step?

Highly unlikely.
Attempts at human cloning are viewed very unfavorably in the scientific community.

Photo of mouse growing a "human ear" - a


shape made of cartilage

What Has Been Cloned So Far?


Somatic Cell Nuclear Transfer
Sheep, Goat, Mouse, Rabbit, Cattle (domestic & wild),
Pig, Horse, Mule, Dog, Cat (domestic & wild), Deer

Embryo Splitting (Twinning)


Sheep, Cattle, Primate (Rhesus)

Transgenic Clones

Cloned transgenic cat containing red fluorescent protein

http://news.aol.com/story/_a/glowing-pig-passes-genes-to-piglets/20080109143909990001?ncid=NWS00010000000001

Idaho Gem, first cloned mule

Surrogate
mother
(horse)

1st try 134 implants 2 pregnancies, both failed


2nd try 113 implantations 14 pregnancies, one birth

http://news.nationalgeographic.com/news/2003/05/0529_030529_muleclone.html

In addition to cloning pets or prized livestock, researchers


are looking to clone transgenic animals
This would allow for more uniform expression of transgenic
genes
Not all transgenic animals express their transgenic genes at
equal levels
Also allows for the rapid expansion to large flocks or herds
of transgenic animals

Piglets clones created by PPL Therapeutics in 2000


The piglets carry a silenced copy of alpha 1,3 galactosyl
transferase, or GT, an enzyme involved in organ rejection
In order to guarantee compatibility a second GT gene must
also be silenced

http://www.newrivervalley.com/biotech/day1.html

Conservation Cloning
Many endangered or extinct animals are being cloned or
considered for cloning
Gaur

Bucardo mountain goat


Mammoth
Quagga
Banteng

Mammoth

Quagga

Bucardo

Gaur

http://www.personal.psu.edu/faculty/t/r/trp2/mammoth.jpeg
http://www.serragaucha.com.br/rocky/zoo.html
http://www.riosmith.net/Gaur004.jpg
http://www1.ceit.es/Asignaturas/Ecologia/EspNaturales/Ordesa/mamiferos.htm#Bucardo

The Future of Cloning


Endangered Species

Noah, a Banteng clone created by Advanced Cell Technologies


Banteng are endangered wild bovine from Southeast Asian
This clone was created from frozen tissue of an animal that
died in 1980

http://www.advancedcell.com/images/Banteng002-sm.jpg

Problems with Cloning


3 Pig clones, born in 2002, died of heart attacks due to adult
clone sudden death syndrome within days of each other by
the time they were 6 months old.
Dolly had a weight problem, telomeres 20% shorter than
normal, she suffered from arthritis, and finally lung cancer
due to an infection for which she was finally euthanized at
age 6yrs.
The success rate ranges from 1 to 3% this contrasts to in
vitro fertilization which has a success rate of 50 to 20%

http://fig.cox.miami.edu/~cmallery/150/gene/cloning.success.jpg

Nearly all clones show some genetic anomalies


Some suffer from placental defects others cardiac defects
Many suffer from large offspring syndrome (LOS)

Normal mouse pup

Cloned mouse pup


suffering from LOS

Why study Animal Cell Biotechnology?


1.

Viral vaccines

2.

Monoclonal antibodies

3.

Recombinant glycoproteins

4.

Hormones, growth factors

5.

Enzymes

Animals in Research

Animals in Research

B1

B2

B3

B4

Animals in Research
FDA Oversight of Drug Development Process
Pre-Clinical Research and Development

Animation: Drug Development Process

Animals in Research
FDA Oversight of Drug Development Process
Pre-Clinical Animal Studies

Animals in Research
Animal Models
Mice
Rats
Zebrafish (3 month generation time, 200
progeny, complete embryogenesis in 120
hrs)
Dogs (lungs and cardiovascular system)
Cats
Pigs (PPL Therapeutics- delete a gene
which causes hyperacute rejection of pigto-human organ transplantation)
Primates (HIV and AIDs research, geriatric
research)

Animals in Research
Alternatives to Animal Models
Cell culture devices
Researchers use cell cultures and computer-generated models
whenever possible, but this doesnt work for looking at an organ
or entire animal

Animals in Research
Regulation of Animal Research
The Three Rs
Reduce the number of higher species (cats, dogs,
primates) used
Replace animals with alternative models whenever
possible
Refine tests and experiments to ensure the most
humane conditions possible

Animals in Research
Veterinary Medicine as Clinical Trials
Treatments for humans may also be useful for treatments
with animals (e.g. the BRCA1 gene found in 65% of human
breast tumors is similar to the BRCA1 gene in dogs)
Hyperthermia + radiation = more effective at killing tumors
Stimulation of cytokines for curing skin cancers

Animals in Research
Bioengineering Mosquitoes to Prevent Malaria
Cloned in a gene that prevents the parasite from traversing
the midgut; blocking the continuation of its life cycle
Developed an antibody that prevents the parasite from
entering the mosquitos salivary gland

Biopharmaceuticals
Scientists are close to finding ways to mass produce
human proteins, antibiotics, and vaccines in cow's
and goat's milk.
This would be an economical and reliable way for
people worldwide to receive these beneficial
products.

Wockhardt launches
indigenous human
recombinant insulin
Mr H. Khorakiwala,
Chairman, Wockhardt
Ltd, with
Dr M. Sahib, Director,
Genomics & Biotech
Research, at the launch
of human recombinant
insulin `Wosulin' in
Mumbai

Improved Foods
Through biotechnology, researchers are
making meat and dairy products better to
eat.
They are improving milk so that 90 percent
of adults who are lactose-intolerant can
drink it.
They also are identifying genes that will
result in less fat in beef and improved flavor
and tenderness.

Transgenic Animals
Transgenic Animal genome has been
changed to carry genes from a different
species

Transgenic animals
Transgenics are genetically modified organisms with DNA
from another source inserted into their genome
A large number of transgenic animals have been created
Mice Cows Pigs Sheep Goats Fish Frogs Insects
Currently, no transgenic animal or animal product is
approved by the FDA or USDA for human consumption

Some of the goals of transgenic animal creation are:


Research into animal and human disease
Improve livestock animals
Use of animals as bioreactors

Transgenic Animal Creation

Microinjection
into the germ line -> transgenic animal

Gene injected into the male


pronuclei

Recombinant Defective Retrovirus

Eggs are infected prior to fertilization


Virus integrates into one of the chromosomes

Linker Based Sperm-Mediated Gene Transfer


(LB-SMGT)

Sperm fertilizes the egg carrying the foreign gene


into the egg where it is incorporated into the genome

Transgenic Animal Generation


Some of the drawbacks of these methods are:
The inserted DNA randomly integrates into the genome
The eggs must be harvested & fertilized in vitro
More than one copy of the gene may get into the genome

Examples of Transgenic Animals

Transgenic Cattle
Dairy cows carrying extra copies of two types of casein
genes produce 13% more milk protein
Not only will this make the milk more nutritious, it would
allow for less milk to make more cheese
Currently the milk from these animals is under FDA review
The important difference between this & other transgenics
is that the DNA added is not foreign

GE Chickens That Don't Transmit Bird Flu


Breakthrough could prevent future bird flu epidemics

www.roslin.ed.ac.uk/public-interest/gm-chickens
Van Eenennaam NIAA 4/16/2013

Omega-3 Pigs
(Pigs cloned after genetically engineering cell)

Nature Biotechnology 24:435-436.

2006

University of Missouri/Massachusetts General Hospital and Harvard Medical School


Van Eenennaam NIAA 4/16/2013

Mastitis-resistant cows (inflammation of


mammary gland)

Nature Biotechnology 23:445-451.

2005

www.ars.usda.gov
Van Eenennaam NIAA 4/16/2013

Fast growing salmon


The founder female was generated in 1989 ~ a quarter century ago
Nature Biotechnology 10:176 181.

1992

University of Toronto/Memorial University of Newfoundland, Canada


Van Eenennaam NIAA 4/16/2013

Fish reach adult size in 16 to 18


months instead of 30 months

Van Eenennaam NIAA 4/16/2013

Timeline of AquAdvantage regulatory process

24+ years from discovery to application?

Year

Event

1989

Founder AquAdvantage fish produced in Canada

1995

FDA review of AquAdvantage salmon begins

2001

First regulatory study submitted by Aqua Bounty Technologies to


U.S. FDA for a New Animal Drug Applications (NADA)

2009

FDA guidance on how GE animals will be regulated


FDA approval of first GE animal pharmaceutical
Final AquAdvantage regulatory study submitted to FDA

2010

FDA VMAC meeting on AquAdvantage salmon (9/20/10)

2011

Political efforts to prevent FDA from regulating GE salmon

2013

AquaBounty has expended over $60 million to bring the


AquAdvantage salmon through the regulatory approval process
thus far (D. Frank, CFO, AquaBounty, pers. comm.)
Still waiting for regulatory decision on AquAdvantage salmon
Delayed approvals diminishing US investment in GE animals
Use of GE animals for food moving to other countries

Van Eenennaam NIAA 4/16/2013

EnviroPig

TM

Transgenic pigs express phytase in their salivary glands


Phytic acid in the pig meal is degraded releasing phosphorus

The phosphorus is absorbed by the pig


Normally the phytic acid/phosphorus complex passes
through the pig and is excreted as waste
Pig waste is a major pollutant & can cause eutrophication of
lakes & streams

http://www.nature.com/news/2005/050221/images/nbt0305-283-I1.jpg

Transgenic Fish
Tilapia
Salmon/trout
Catfish

Can grow up to 6 times faster than wildtype fish


Most have extra copies of growth hormone (GH) gene

Transgenic
Wildtype

http://www.nature.com/nbt/journal/v19/n6/images/nbt0601_500a_I1.jpg

The transgene used to increase growth utilizes an


antifreeze protein promoter connected to the GH cDNA

Antifreeze promoter
from pout

As water temperature drops the GH gene is turned on


The fish continue to grow when normally they would not

http://pubs.acs.org/hotartcl/chemtech/99/jun/fletcher.html

Concerns if these supersized transgenic fish got loose


Transgenic fish are farm-raised, isolated from wild stocks
But even during farming of wildtype fish, escapes happen
frequently (~14 million/yr)
What would happen if a large number of transgenic escaped
& started breeding with wild fish?

http://pewagbiotech.org/buzz/index.php3?IssueID=10

In experiments, transgenic males mated 3x more


frequently than the smaller wild males
Offspring of transgenic males lived <70% as long as
wild males
Could lead to a decline of the wild fish population &
endanger a species as whole

Antifreeze Proteins (AFP)


AFPs lower the freezing temperature of blood & fluids
Trout normally do not survive in water below 0.6C
Transgenic trout containing an AFP gene & promoter can
survive in waters as cold as 1.2C

wild
transgenic

+Antifreeze

http://pubs.acs.org/hotartcl/chemtech/99/jun/fletcher.html

Animal Bioreactors
Pharming

1997, Tracy the sheep, the first transgenic animal to


produce a recombinant protein drug in her milk
alpha-1-antitrypsin (AAT) treatment for emphysema &
cystic fibrosis
Created by PPL Therapeutics & The Roslin Institute

http://nolswf.bbc.net.uk/science/genes/gene_safari/pharm/a_pharming.shtml

Nexia Biotechnologies transfered the silk gene from Orb


spiders into goats
Webster and Peter
The resulting male goats were used to sire silk-producing
female goats

Each goat produces several grams of silk protein in her


milk
The silk is extracted, dried to a white powder, and spun
into fibers
The fibers are stronger and more flexible than steel
Transgenic male kids
carrying silk gene

GTC Biotherapeutics has received approval to sell human


anti-thrombin (ATryn) purified from goats milk in Europe
Technology is not restricted to cows, goats, & sheep

There is interest in using rabbits since housing costs are


significantly less & generation time is faster
Chickens which produce recombinant drugs in their eggs
have been produced by The Roslin Institute

Other Types of Transgenic Animals

Transgene ->
Gene coding
for a growth
hormone

ANDi, the first transgenic primate born in January, 2000


224 unfertilized rhesus eggs were infected with a GFP virus
~Half of the fertilized eggs grew and divided
40 were implanted into twenty surrogate mothers
five males were born,two were stillborn
ANDi was the only live monkey carrying the GFP gene
http://www.ohsu.edu/unparchive/2001/011001andi.shtml

Alba, the EGFP (enhanced GFP) bunny


Created in 2000 as a transgenic artwork
http://www.ekac.org/gfpbunny.html#gfpbunnyanchor

Transgenic Pigs Pass on the Transgene

http://news.aol.com/story/_a/glowing-pig-passes-genes-to-piglets/20080109143909990001?ncid=NWS00010000000001

GloFish, originally developed in Singapore as a way to monitor


water pollution
The normally black-and-silver zebrafish was turned green or
red by inserting various versions of the GFP gene
Glofish are on sale throughout the US except in California
Glofish retail for about $5 per fish. Normal zebrafish cost
around one tenth of the price

http://www.nus.edu.sg/corporate/research/gallery/research12.htm

Mouse Knock-out Technology

Gene Targeting

Knock-out technology allows for the specific loss of a gene


in mice
Allows for the function of the KOd gene to be deduced from
the defects seen in the mice
can be used to mimick some disease
Unlike traditional transgenics the trangene is targeted to a
specific site in the DNA of the mouse

Mouse Knock-outs require embryonic stem (ES) cells


These are derived from the inner cell mass (ICM) of a
blastocyst (the ICM is what will become the fetus)
ES cells are pluripotent meaning they can become all the
different cell types found in an adult
http://cba.musc.edu/SC_COBRE/CORE-B/Resources-B.htm

Blastocyst Injection

Blastocyst

ES cells

http://tasq.uq.edu.au/blasto.html

Chimeric mouse
The brown fur comes from ES cells injected
into the blastocyst of an albino mouse

http://bunseiserver.pharm.hokudai.ac.jp/gihou/knockout.html

Some Examples of Knockout Mice

p27 knockout mouse

p27 knockout mouse is bigger than the control


This is not due to obesity, but the skeletal structure is
increased in size (everything about the mouse is larger)

http://www.bioreg.kyushu-u.ac.jp/saibouE.html

normal

knockout

GDF8 (Myostatin) knockout mouse


Over twice the muscle mass of a wildtype mouse

http://www.bbc.co.uk/science/genes/gene_safari/wild_west/bigger_and_better02.shtml

Naturally Occurring GDF8 Mutants

http://www.canada.com/victoriatimescolonist/story.html?id=67f15c17-2717-4022-bb76-1b982456e793&k=94653
http://www.bbc.co.uk/science/genes/gene_safari/wild_west/bigger_and_better02.shtml

FGF5 knockout mouse has long, angora-like hair

http://www.med.uni-jena.de/ivm/deutsch/method/method_7.htm

Transgenic Techniques
Embryonic Stem Cell Method

Transgenic Techniques
Pronuclear Injection
Animation of Pronuclear Injection

Transgenic Techniques
Making clones of a transgenic animal
Animation: Using
SCNT to make
transgenic goat

Transgenic Applications
Increased Production Efficiency: Transgenic
Growth Hormones

Transgenic Applications
Improved Food Safety and Quality: longer
shelf life

Transgenic Applications
Improved Food Safety and Quality: lactose
intolerance

Transgenic Applications
Increase Nutritional Content:
Lactoferrin

Transgenic Applications
Increased Production Efficiency:
lactational performance

boost

Transgenic Applications
Disease Resistant Animals less susceptible to
mastitis

Transgenic Applications
Disease Resistant Animals less susceptible to
mad cow disease

Transgenic Applications
Decreased Environmental Impact

Transgenic Animals
Transgenic Animals as Bioreactors
Biosteel otherwise known as spider silk, cloned into goat
milk (silkmilk goats)
Goats reproduce faster than cows and are cheaper than
cows
Hens also make good bioreactors in that they are cheap and
a lot of eggs are produced at one time

Transgenic Animals
Knock-outs: A Special Case of
Transgenesis
A specific gene is disrupted or removed
such that it is not expressed
Procedure: DNA is modified, it is added
to embryonic stem cells, where it
undergoes homologous recombination.
The modified ES cells are then
introduced into normal embryo. The
embryo is implanted in an incubator
mother. The offspring is a chimera. It
may take several generations of
crossbreeding are required to produce
animals that are complete knock-outs.
Breast cancer mouse

Producing Human Antibodies in Animals


Production of Monoclonal
antibodies (Mabs)

Used to treat cancer, heart


disease, and transplant
rejection
HUMANIZED monoclonal
antibodies were developed to
prevent the human antimouse antibody (HAMA)
response

Other pharma products

Antibodies (more than 10 billions market)


Interferons
Hormones
Eritropoietine
Inmunoadhesines
Vaccines

Transplant Organs for Humans

Inadequate supplies of human organs for


transplantation result in more than
25,000 deaths annually.
Researchers are studying ways to
develop organs in animals suitable to be
transplanted into humans until human
organs become available.
Especially promising are pig organs!!!

Tissue Engineering
Researchers can transfer human body cells to
animal cells to produce cells capable of
forming virtually any cell type, including tissue
This means that patients with life-threatening
illnesses, such as heart disease, spinal cord
injury, or arthritis, could have healthy tissue
grown from their own cells in animals to
replace their damaged tissue without their
immune system rejecting the tissue.

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