1. TRANSGENIC AND GENOME
EDITED ANIMALS,
APPLICATION AND ETHICAL
ISSUES
Submitted by: Pooja Jangir (221243)
Submitted to: Dr. Ramgopal
2. Difference
TRANSGENIC ANIMALS
• Modification done by introduction
of foreign gene.
• Methods: Microinjection, viral
vector
• Random integration of foreign DNA
with less precision and control.
• Example: GloFish, Transgenic mice,
Transgenic livestock,
AquAdvantage salmon.
GENOME EDITED ANIMALS
• Modification is done within their
own genome.
• Method: genome editing tools like
CRISPER-Cas9, TALENs, ZFN etc.
• Targeted changes and high
precision
• Example: Disease models in mice,
Pigs with organ transplant
potential, Mosquitoes resistant to
malaria, Hornless cattle.
3. GloFish (TRANSGENIC ANIMAL)
• Modified Zebra fish that exhibit vibrant
fluorescent colors.
• Insertion of fluorescent protein genes
from organisms like jellyfish or sea
anemones into zebra fish genome.
• Green Fluorescent Protein (GFP) gene
from Aequorea Victoria (jellyfish) is
inserted into zebra fish embryo using
microinjection.
• Application:
• Decorative pets
• To study gene expression, genetic
inheritance
4. TRANSGENIC MICE
• In 1987, the first transgenic mouse producing sheep β-lactoglobulin in
milk was generated through pronuclear injection.
• Alzheimer’s disease models: Mutated human gene like APP (amyloid
precursor protein or the presenilin gene is expressed that cause
development of amyloid plaques and neurofibrillary tangles similar to
Alzheimer’s patients to test potential therapies.
• Cancer research models
• Diabetes studies
• Obesity and metabolic disorders
• Heart disease models
5. TRANSGENIC LIVESTOCK
• Transgenic goats producing human antithrombin in their milk that has
anticoagulant properties.
• This proein from their milk can be harvested and purified that can be
used as medicine in patients with hereditary antithrombin deficiency
or risk of blod clot during surgeries.
• Cost effective and efficient method to produce therapeutic protein.
6. AquAdvantage Salmons
• In Atlantic salmon, growth hormone gene from Chinkook salmon
(larger and faster growing fish) and promotor sequence to control
expression from eel-like fish called ocean pout is introduced.
• This ensures growth hormone activation throughout the year rather
than seasonally promoting continuous growth.
• Advantage: AquAdvantage salmon with acelerated growth, reaching
market size in half the time compared to conventional Atlantic
salmon.
7. Species Protein Genetic Engineering Technology Reference
Rabbit Human α-glucosidase Pronuclear Injection (Van den Hout et al. 2001)
Human plasminogen activator Pronuclear Injection (Song et al. 2016)
C1 esterase inhibitor Pronuclear Injection (Van Veen et al. 2012)
Goat Human Granulocyte-Colony Stimulating Factor Pronuclear Injection (Ko et al. 2000)
Human Glycoprotein α-fetoprotein SCNT (Parker et al. 2004)
CuZn and EC- SOD SCNT (Lu et al. 2018)
Human Lactoferrin TALENs/SCNT (Cui et al. 2015)
Antithrombin (ATryn) Pronuclear Injection (Adiguzel et al. 2009)
Cow Human Lactoferrin Pronuclear Injection (Van Berkel et al. 2002)
SCNT (Wang et al. 2017)
Human Serum Albumin TALENs/ SCNT (Luo et al. 2016)
Pig Human Blood Clotting Factor VIII Pronuclear Injection (Paleyanda et al. 1997)
Human Erythropoietin Pronuclear Injection (Park et al. 2006)
Human Furin Enzyme and Factor IX SCNT (Zhao et al. 2015)
Chicken Human lysosomal Acid Lipase (Kanuma) Viral Vector (Sheridan 2016)
Human interferon α- 2b Viral Vector (Rapp et al. 2003)
Human Erythropoietin Viral Vector (Kwon et al. 2018)
Human Interferon β PGCs/ CRISPR/Cas9 (Oishi et al. 2018)
Table I:
Examples of transgenic animal produced recombinant human proteins in milk or eggs.
Hay, A. N., Farrell, K., Leeth, C. M., & Lee, K. (2022). Use of genome editing techniques to produce transgenic farm
animals. Recent Advances in Animal Nutrition and Metabolism, 279-297.
8. GENOME EDITED DISEASE MICE MODELS
• Cystic Fibrosis (CF) mice models: Specific mutations in CFTR gene
through CRISPER-Cas9 to initiate symptoms similar to human CF.
• Cancer models: Mutations in tumor suppressor genes (e.g., TP53) or
oncogenes (e.g., KRAS) induce cancer in mice which helps to
understand the molecular mechanism of cancer development,
progression and response to treatments.
• Neurological disorder models
• Cardiovascular disease models
9. PIGS AS POTENTIAL ORGAN DONORS
• Removal or inactivation of retrovirus gee that are present in pigs
naturally and can pose a risk of transmission to human receiving pig’s
organs.
• Editing genes related to immune response or modification of surface
proteins to reduce the chance of organ rejection.
10. MALARIA RESISTANT MOSQUITO
• Anopheles gambiae NF-κB transcription factor Rel2 (AgRel2) gene is
involved in immune response is modified in such a way that it
impedes the development and transmission of malaria parasite.
• Modification in the gene that can enhance its expression can make
the immune response better than before making mosquito less
susceptible to parasite.
11. HORNLESS ‘Polled’ CATTLE
• Primary gene for horn growth is PIS (Polled Intersex Syndrome) gene
which by introduction of gRNAs and Cas9 enzyme in bovine embryo
can result in inactivation of PIS gene or its expression is disrupted.
• This prevents development of hornless cattle which offers ease of
handling, reduced aggression.
12. ETHICAL ISSUES
• Animal welfare: Mice or other animals used in laboratories for
creating transgenic or genome-edited models may experience
discomfort or health issues .
• Environmental impact: Genetically modified fish released into
ecosystems might interbreed with wild populations, potentially
altering the genetic makeup or ecological balance of the wild species.
• Unintended consequences
• Ownership and patenting
• Societal and cultural concerns: Raising questions about respect for
cultural values and ethical boundaries.
13. REFERENCE
• Knight, J. (2003). GloFish casts light on murky policing of transgenic
animals. Nature, 426(6965), 372.
• Hay, A. N., Farrell, K., Leeth, C. M., & Lee, K. (2022). Use of genome editing
techniques to produce transgenic farm animals. Recent Advances in Animal
Nutrition and Metabolism, 279-297.
• Clifford, H. (2014, October). AquAdvantage® Salmon-a pioneering
application of biotechnology in aquaculture. In BMC Proceedings (Vol. 8,
No. 4, pp. 1-2). BioMed Central.
• Cozzi, E., & White, D. J. (1995). The generation of transgenic pigs as
potential organ donors for humans. Nature medicine, 1(9), 964-966.
• Carlson, D. F., Lancto, C. A., Zang, B., Kim, E. S., Walton, M., Oldeschulte, D.,
... & Fahrenkrug, S. C. (2016). Production of hornless dairy cattle from
genome-edited cell lines. Nature biotechnology, 34(5), 479-481.
