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A transgenic animal is an animal whose genome has been altered by the inclusion

of
foreign genetic material. An organism s genome is the set of genes that ensure the
transmission
of hereditary material. The foreign genetic material is introduced to the organi
sm through
recombinant DNA technology. The purpose of adding a new gene to an organism s
genome is to have the organism produce a protein or set of proteins that it did
not produce before
the gene was added.
Transgenic History:
Even before the advancement of molecular biology, farmers selectively bred their
cattle to make them more marketable. For example, a farmer bred a male cow that
was very large with a female that produced the most milk, hoping that the calf
would grow up to be large to yield high amounts of meat, or as a female produce
the
most milk.
The underlying principle in the production of transgenic animals is the introduc
tion of a foreign gene or genes into an animal (the inserted genes are called tr
ansgenes). The foreign genes "must be transmitted through the germ line, so that
every cell, including germ cells, of the animal contain the same modified genet
ic material."(Germ cells are cells whose function is to transmit genes to an org
anism's offspring.)
Transgenic Cattle:
Cattle is a combined term used for oxes, bulls, buffalos, cows, etc. Cattle are
farmed for beef, veal, dairy, leather, etc. Majorly, they are raised as dairy an
imals universally for mild and other dairy products like cheese, butter, yogurt
etc and as livestock for meat in many parts of the world. Thus, trait enhanceme
nt of cattle can be of great value due to many nutritional and economic value at
tached to it. By recombinant DNA technology, cattle can be made disease resista
nt, elevate milk quality and quantity as well as meat.

Production of trangenic cattle:


To date, there are three basic methods of producing transgenic cattle-
1. DNA microinjection
2. Retrovirus-mediated gene transfer
3. Embryonic stem cell-mediated gene transfer

1. DNA Microinjection
Gene transfer by microinjection is the predominant method used to produce transg
enic farm animals. Since the insertion of DNA results in a random process, trans
genic animals are mated to ensure that their offspring acquire the desired trans
gene. However, the success rate of producing transgenic animals individually by
these methods is very low and it may be more efficient to use cloning techniques
to increase their numbers.
This method involves: Transfer of a desired gene construct (of a single gene or
a combination of genes that are recombined and then cloned) from another member
of the same species or from a different species into the pronucleus of a reprod
uctive cell. The manipulated cell, which first must be cultured in vitro (in a l
ab, not in a live animal) to develop to a specific embryonic phase, is then tran
sferred to the recipient female
The mouse was the first animal to undergo successful gene transfer using DNA mic
roinjection.
There are other techniques apart from microinjection, such as- electroporation,
sonoporation, optical transfection, etc.
2. Retrovirus-Mediated Gene Transfer
A retrovirus/adenovirus is a virus that carries its genetic material in the form
of RNA rather than DNA. This method involves:
Retroviruses used as vectors to transfer genetic material into the host cell,
resulting in a chimera (A chimera is an animal that consists of two or more tis
sues that have different genetic compositions produced by genetic engineering. T
his means that some of the cells are transgenic and some of the cells in the org
anism are not.)
Chimeras are inbred for as many as 20 generations until homozygous (carrying
the desired transgene in every cell) transgenic offspring are born.
The method was successfully used in 1974 when a simian virus was inserted into m
ice embryos, resulting in mice carrying this DNA.
3. Embryonic Stem Cell-Mediated Gene Transfer
This method involves:
Isolation of totipotent stem cells (stem cells that can develop into any type
of specialized cell) from embryos
The desired gene is inserted into these cells
Cells containing the desired DNA are incorporated into the host's embryo, res
ulting in a chimeric animal
Unlike the other two methods, which require live transgenic offspring to test fo
r the presence of the desired transgene, this method allows testing for transgen
es at the cell stage.
4. Homologous recombination:
Is also referred to as gene targeted knockout. this technique involves: introduc
tion of a transgene to a targeted location on the native DNA. the targeted gene
is usually prevented from expression (is knocked out).

Examples of Transgenic cattle:


1) One of the most notable transgenic cattle is Herman the Bull engineered by Ge
n Pharm International, CA. Herman was engineered to carry a gene for lactoferrin
, hoping that his female offspring would produce the protein in their milk and t
hus alleviate the need for human babies to drink formula or mother s milk unnatura
lly low in this protein. Without the lactoferrin, human babies cannot survive on
cow s milk. Studies on the milk of the transgenic cattle showed that the lactofer
rin production is high enough to meet the needs of human children.

2) Rosie (in 1997) was the first successful transgenic cow to produce modified m
ilk containing the human proteins L-lactalbumin, an important nutritional protei
n rich in amino acids and particularly useful in feeding premature babies.
The is more nutritionally balanced than natural cow s milk and more suitable to ba
bies and elderly who have specific dietary needs.
Applications:
1. Modification of milk
Quantity: Administration of recombinant bovine somatotropin (rbST) has signific
antly increased milk production in cattle and led to development of transgenic c
attle carrying and expressing fusion genes (eg: metallothionein-I) coding for in
creased milk production.
Quality: By elevating the major components of milk (saturated fat, protein & cal
cium), health and growth of the consumer can be mpacted. Increasing one of Casei
n components in milk could increase production of cheese or yogurt. Increasing b
eta casein content could result in thermal stability and shelf life of milk
2. Quality of meat:
By transgenic technology, grawoth factors, growth factor receptors and growth mo
dulators can be manipulated to impact growth o the animal potentially used for m
eat consumption purposes. Since there is a lot of demand for lean meat by consum
ers, fat and cholesterol content in meats could be lowered. Beneficial Omega-3-f
atty acid gene from fish could be introduced into livestock.
3. Disease resistance:
By introducing specific genes into livestocks, disease resistance can be increas
ed. Potential areas of investigation include resistance to parasites like nemato
des, viral or bacterial organisms like foot and mouth virus, clostridium, strept
ococcus, etc, genetic diseases like mule foot and bovine leukocyte adhesion defi
ciency (BLAD)
4. Synthesis of various compounds:
Transgenic cattle can be used for production of different therapeutic protiens f
or human clinical purposes (biopharming). Through genetic engineering ti has bec
ome possible to produce any protin from any animal, plant or bacterial species.
The site of expression could be blood, urine or milk. The proteins could help to
treat phenylketonuria (PKU) and cystic fibrosis, as well as insulin,growth horm
one, and blood anti-clotting factors can be produced. Human hemoglobin has been
produced in swine s blood.
Raising a cow that produces much-needed pharmaceutical components in its milk co
uld be more economical and accessible than buying drugs.

Disadvantages:
1. Production and price of a transgenic animal is costly
2. the successful animals produced that carry the desired traits are few.
3. Ethical and legal issues involving these animals are very high.

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