Which Of The Following Best Defines The Term Transgenic Animal

Transgenic animals

Definition

A transgenic beast is one whose genome has been contradistinct by the transfer of a gene or genes from another species or breed.

The photograph shows two transgenic mice positioned either side of a manifestly mouse. The transgenic mice have been genetically modified so that they behave a green fluorescent protein which glows green nether blue light. Credit: Ingrid Moen et alet al., BMC Cancer, 12/21 (2012), 1-10.

Importance

Transgenic animals are routinely used in the laboratory every bit models in biomedical research. Over 95 per cent of those used are genetically modified rodents, predominantly mice. They are important tools for researching homo disease, existence used to sympathize gene function in the context of affliction susceptibility, progression and to determine responses to a therapeutic intervention.

Mice have also been genetically modified to naturally produce human antibodies for apply as therapeutics. 7 out of the eleven monoclonal antibody drugs approved by the FDA between 2006 and 2011 were derived from transgenic mice.

Transgenic subcontract animals are also existence explored as a means to produce large quantities of complex human proteins for the treatment of human affliction. Such therapeutic proteins are currently produced in mammalian cell-based reactors, but this production process is expensive. In 2008, for case, the building of a new cell-based manufacturing facility for one therapeutic protein was estimated to cost over United states of america$500 million. A cheaper option would exist to develop a ways to produce recombinant proteins in the milk, claret or eggs of transgenic animals. Progress in this area, nonetheless, has been slow to-engagement. Only two biomedical products have so far received regulatory approval. The first is human antithrombin Iii, a therapeutic protein produced in the milk of transgenic goats, which is used to forbid clots in patients with hereditary antithrombin deficiency receiving surgery or undergoing childbirth. A relatively small herd of goats (about 80) tin supply plenty human antithrombin III for all of Europe. The 2d production is a recombinant human being C12 esterase inhibitior produced in the milk of transgenic rabbits. This is used to treat hereditary angiodema, a rare genetic disorder which causes claret vessels in the blood to aggrandize and cause skin swellings.

Discovery

The ability to produce transgenic animals is reliant on a number of components. I of the first things needed to generate transgenic animals is the ability to transfer embryos. The offset successful transfer of embryos was achieved by Walter Heape in Angora rabbits in 1891. Another of import component is the power to manipulate the embryo. In vitro manipulation of embryos in mice was offset reported in the 1940s using a culture arrangement. What is also vital is the ability to manipulate eggs. This was fabricated possible through the efforts of Ralph Brinster, attached to the University of Pennsylvania, who in 1963 devised a reliable system to culture eggs, and that of Teh Ping Lin, based at the California School of Medicine, who in 1966 outlined a technique to micro-inject fertilised mouse eggs which enabled the accurate insertion of foreign Dna.

The first genetic modification of animals was reported in 1974 past the virologist Rudolph Jaenisch, so at the Salk Institute, and the mouse embryologist Beatrice Mintz at Fox Chase Cancer Center. They demonstrated the feasibility of modifying genes in mice by injecting the SV40 virus into early-stage mouse embryos. The resulting mice carried the modified cistron in all their tissues. In 1976, Jaenisch reported that the Moloney Murine Leukemia Virus could also be passed on to offspring by infecting an embryo. 4 years later, in 1980, Jon Gordon and George Scango together with Frank Ruddle, announced the nascence of a mouse born with genetic material they had inserted into newly fertilised mouse eggs. By 1981 other scientists had reported the successful implantation of foreign DNA into mice, thereby altering the genetic makeup of the animals. This included Mintz with Tim Stewart and Erwin Wagner at the Play tricks Hunt Cancer Middle in Philadelphia; Brinster and Richard Palmiter at the University of Washington, Seattle; and Frank Costantini and Elizabeth Lacy at Oxford University.

Such work laid the basis for the cosmos of transgenic mice genetically modified to inherit particular forms of cancer. These mice were generated every bit a laboratory tool to better understand the onset and progression of cancer. The advantage of such mice is that they provide a model which closely mimics the human trunk. The mice not just provide a means to proceeds greater insight into cancer but also to exam experimental drugs.

Application

Transgenic animals are animals (most normally mice) that take had a foreign gene deliberately inserted into their genome. Such animals are virtually ordinarily created by the microinjection of Dna into the pronuclei of a fertilised egg which is subsequently implanted into the oviduct of a pseudopregnant surrogate mother. This results in the recipient animate being giving nascency to genetically modified offspring. The progeny are and so bred with other transgenic offspring to establish a transgenic line. Transgenic animals tin can also exist created by inserting DNA into embryonic stem cells which are and then micro-injected into an embryo which has adult for v or six days after fecundation, or infecting an embryo with viruses that carry a Deoxyribonucleic acid of involvement. This final method is commonly used to manipulate a single gene, in most cases this involves removing or 'knocking out' a target gene. The end upshot is what is known as a 'knockout' animal.

Since the mid-1980s transgenic mice have become a central model for investigating disease. Mice are the model of pick not only because there is all-encompassing analysis of its completed genome sequence, just its genome is similar to the human. Moreover, physiologic and behavioural tests performed on mice can exist extrapolated direct to homo disease. Robust and sophisticated techniques are likewise hands available for the generic manipulation of mouse cells and embryos. Another reward of mice is the fact that they accept a short reproduction cycle. Other transgenic species, such as pig, sheep and rats are besides used, but their employ in pharmaceutical enquiry has so far been limited due to technical constraints. Recent technological advances, even so, are laying the foundation for wider adoption of the transgenic rat.

Transgenic rodents play a number of critical roles in drug discovery and development. Importantly, they enable scientists to study the function of specific genes at the level of the whole organism which has enhanced the study of physiology and disease biology and facilitated the identification of new drug targets. Due to their similarity in physiology and gene function between humans and rodents, transgenic rodents can be developed to mimic human disease. Indeed, an assortment of transgenic mice models have been produced for this purpose. Mice are being used as models, for example, to report obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, ageing, Alzheimer'south disease and Parkinson'southward disease. They are also used to study different forms of cancer. In addition, transgenic pigs are being investigated as a source of organs for transplants, which if proven clinically safe could overcome some of the severe donor organ shortages. The evolution of transgenic animals has recently been transformed by the emergence of the new cistron editing tool CRISPR which greatly reduced the number of steps involved in the cosmos of transgenic animals, making the whole process much faster and less plush.

This section on transgenic mice was jointly written by Lara Marks and Dmitriy Myelnikov. For more information see D. Myelnikov, 'Transforming mice: technique and communication in the making of transgenic animals, 1974-1988', unpublished PhD, Cambridge Academy, 2015.

Transgenic animals: timeline of key events

Smithies was a geneticist and physical biochemist. He first made his mark in 1955 through his invention of starch gel electrophoresis, a technique used to written report human protein variation. Afterwards on, in the 1980s he adult a method for targeted gene replacement in mice, now known as gene targeting, for which he was awarded the Nobel Prize for Medicine in 2007. His method facilitated the creation of thousands of lines of mice carrying desired genetic mutations. Such mice are now widely used to investigate the function of many different genes in man health and disease. 1925-06-23T00:00:00+0000 Founded by Clarence Lilliputian, one of the leading researchers into genetic differences governing the rejection of foreign tissues. 1929-01-01T00:00:00+0000 Ruddle helped pioneer human gene mapping and established many of the techniques and a framework for setting up the Human being Genome Projection. He generated, with Jon W. Gordon and George Scango the first successful transgenic mouse. This heralded the evolution of genetically modified animals as inquiry models to investigate the function of genes and genetic cause of illness. Ruddle besides discovered, with William McGinnis, the first human homeobox genes, of import regulators of gene development. 1929-08-19T00:00:00+0000 Clark was a molecular biologist who used genetic technology to create the first sheep capable of producing big quantities of human protein. The sheep, Tracy, born in 1990, provided 35g of the alpha-1-antitrypsin in each litre of her milk. The protein is used in the treatment of cystic fibrosis. Clark also managed to develop the first big transgenic animal, a sheep, in which a prion poly peptide cistron had been improved. 1951-09-18T00:00:00+0000 1974-01-01T00:00:00+0000 The mice were made with the help recombinant Dna technology. JW Gordon, GA Scangos, DJ Plotkin, J A Barbosa, FH Ruddle, 'Genetic transformation of mouse embryos by microinjection of purified Dna', PNAS USA, 77 (1980), 7380–4. 1980-09-01T00:00:00+0000 M Capecchi, 'Loftier efficiency transformation past direct microinjection of Deoxyribonucleic acid into cultured mammalian cells', Cell, 22/2 (1980), 479-88. 1980-11-01T00:00:00+0000 The experiment proved it was possible to transfer a cloned gene into germ-line cells and for the gene to exist subsequently transmitted into the offspring. This was the showtime step towards the evolution of transgenic mice. F Costantini, E Lacy, 'Introduction of a rabbit b-globin gene into the mouse germ line', Nature, 294 (1981), 92–iv. 1981-11-05T00:00:00+0000 1982-12-01T00:00:00+0000 The course is started at Cold Harbour Laboratory together with collaborators from other centres. 1983-01-01T00:00:00+0000 These are created with the objective of studying self-tolerance. 1985-01-01T00:00:00+0000 Capecchi, M, 'Site-directed mutagenesis by gene targeting in mouse embyo-derived stem cells', Cell, 51/3 (1987), 503-12. 1987-11-06T00:00:00+0000 This patent is filed on the footing of work reported in One thousand Brüggeman, HM Caskey, C Teale, H Waldmann, Williams, Surani, and MS Neuberger, A repertoire of monoclonal antibodies with human heavy chains from transgenic mice, Proc Natl Acad Sci U.s.a., 86 (Sept 1989), 6709-xiii. 1988-01-01T00:00:00+0000 USPTO patent 4,736,866 awarded for transgenic mouse with activated oncogenes created past Philip Leder and Timonthy A Stewart at Harvard Academy. The two scientists isolated a gene that causes cancer in many mammals, including humans, and inserted it into fertilised mouse eggs. The aim was to genetically engineer a mouse as a model for furthering cancer inquiry and the testing of new drugs. It was the first animal ever given patent protection in the USA. 1988-04-12T00:00:00+0000 Mouse genetated with genes knocked out that produce the enzyme Deoxyribonucleic acid methyltransfgerase involved in Dna methylation. E. Li, T.H. Bestor, R. Jaenisch, 'Targeted mutation of the DNA methyltransferase gene results in embryonic lethality', Jail cell, 69/half-dozen (1992), 915-26. 1992-06-12T00:00:00+0000 3 groups of scientists separately report the successful generation of different strains of transgenic mice for the generation of human monoclonal antibodies. Ii of the teams are based in biotechnology companies: GenPharm (led by Nils Lonsberg), Cell Gensys (led by Larry Green) , and the other involved a collaboration (led by Marian Bruggemann and Michael Neuberger) betwixt scientists at the Laboratory of Molecular Biology, Braham Institute and the University of Cologne. 1994-01-01T00:00:00+0000 Dolly the sheep was created by cloning an adult jail cell. This was washed by transferring the nucleus of an adult sheep'southward cell to the nucleus of an unfertilised egg cell. Information technology took 277 attempts to achieve success. The work was carried out past Keith Campbell, Ian Wilmut and colleagues at the Rosilin Institute, PPL Therapeutics and the Ministry of Agronomics. 1996-07-05T00:00:00+0000 The sheep, Polly, was produced by the same scientists who cloned Dolly the sheep. Polly was one of 6 cloned lambs which had human genes inserted. The gene that was transferred was linked to so human blood clotting cistron IX. Such genetic engineering was done to demonstrate the potential of such recombinant DNA technology combined with creature cloning. It was done in the promise that one twenty-four hour period transgenic animals might provide pharmacological and therapeutic proteins and transplant organs to treat human diseases. The work was published in AE Schnieke; et al, 'Man factor IX transgenic sheep produced past transfer of nuclei from transfected fetal fibroblasts', Scientific discipline, 278/5346 (1997), 2130–33. 1997-07-09T00:00:00+0000 Dolly the sheep was created by cloning an adult jail cell. This was done by transferring the nucleus of an adult sheep's prison cell to the nucleus of an unfertilised egg jail cell. It took 277 attempts to achieve success. 2003-02-14T00:00:00+0000 Clark was a British molecular biologist who used genetic technology to create the first sheep capable of producing big quantities of homo protein. The sheep, Tracy, built-in in 1990, provided 35g of the alpha-i-antitrypsin in each litre of her milk. The protein is used in the treatment of cystic fibrosis. Clark also managed to develop the first large transgenic animal, a sheep, in which a prion protein gene had been improved. 2004-08-12T00:00:00+0000 Panitumumab (Vectibix) was approved by the FDA for the treatment of patients with EGFR-expressing metatastic colorectal cancer. The drug is a fully human monoclonal antibody created with transgenic mice. It was adult by Agensys with Amgen. 2006-09-27T00:00:00+0000 The Prize was awarded to to Mario Capecchi, Martin Evans and Oliver Smithies. Their piece of work fabricated it possible to alter specoific genes in the germline of mammals which could produce offspring that carried and expressed the modified gene. Their method is commonly called knockout technology. This has given scientists the means to study the role of specific genes in evolution, physiology and pathology. 2007-01-01T00:00:00+0000 Ruddle helped pioneer human cistron mapping and established many of the techniques and a framework for setting up the Human Genome Projection. He as well generated, with Jon Due west. Gordon and George Scango the start successful transgenic mouse. This heralded the development of genetically modified animals as research models to investigate the function of genes and genetic crusade of disease. Ruddle also discovered, with William McGinnis, the first human homeobox genes, important regulators of gene evolution. 2013-03-10T00:00:00+0000 A pioneer of antibody engineering, Neuberger developed some of the start techniques for the generation of chimeric and humanised antibodies. He too helped create the first transgenic mice for the production of man monoclonal antibodies. His piece of work paved the manner for the generation of safer and more effective monoclonal antibody drugs. 2013-10-26T00:00:00+0000 The pigs, a minor breed known every bit Bama, had some of their genes disabled. They were developed for use in studying stem cells, gut microbiota, and Laron syndome, a type of dwarfism acquired by a mutation in the human GHR gene. The announcement was fabricated at Shenzhen International Biotech Leaders Meridian. 2015-09-23T00:00:00+0000 The aim was to to inactivate 62 endogenous retroviruses in the pig embryos. All pigs take these viruses embedded in their genomes. The presence of such viruses, which can transmit diseases similar cancer, is a major hurdle to the transplant of squealer organs into humans. The gene editing work was carried out by the geneticist George Church of Harvard Medical Schoolhouse. He and his team presented the results to the US National Academy of Sciences. 2015-10-05T00:00:00+0000 Smithies was a British-born American geneticist and physical biochemist. He kickoff made his mark in 1955 through his invention of starch gel electrophoresis, a technique used to written report human protein variation. Later on, in the 1980s he adult a method for targeted gene replacement in mice, at present known as gene targeting, for which he was awarded the Nobel Prize for Medicine in 2007. His method facilitated the creation of thousands of lines of mice carrying desired genetic mutations. Such mice are now widely used to investigate the role of many different genes in human wellness and disease. 2017-01-10T00:00:00+0000 Collaborative enquiry carried out by scientists at University of Edinburgh, University Higher London and Imperial College. 2017-04-20T00:00:00+0000 A team of scientists managed to engineer mice to express Cas9 and a Dna sequence needed for the gene drive, called a cassette, which encoded a guide RNA that targets a sequence in the TYR gene which affects the mouse glaze colour. This provided a means of tracking the frequency of the genetic modification over several generations of mice. The work was published in HA Grunwald et al. 'Super-Mendelian inheritance mediated past CRISPR–Cas9 in the female mouse germline', Nature, January 23, 2019. 2019-01-23T00:00:00+0000 A team of surgeons led by Robert Montgomery at New York Academy Langone Health attached the organ to a brain-expressionless individual who was beingness maintained on a ventilator. Although the kidney remained outside the body, it worked ordinarily, making urine and creatinine, a waste production. 2021-09-25T00:00:00+0000 The transplant was performed on David Bennett, a 57 year sometime, by doctors at the University of Maryland Medical Center. The centre was taken from a pig that had been genetically modified to knock out several genes that would take led to the organ beingness rejected by Mr Bennett'due south immune system. The handling was considered the last promise for saving Mr Bennett who had heart failure. Mr Bennett was reported to be doing well three days after the performance just died after two months. The team who performed the transplant was led by Muhammad Mohiuddin. 2022-01-11T00:00:00+0000

Date	Event	People	Places
23 Jun 1925	Oliver Smithies was born in Halifax, United Kingdom	Smithes	University of Washington, University of North Carolina
1929	Jackson Memorial Laboratories established to develop inbred strains of mice to study the genetics of cancer and other diseases		Jackson Memorial Laboratoroies
nineteen Aug 1929	Frank Ruddle was built-in in West New York, New Jersey	Ruddle	Yale University
xviii Sep 1951	Anthony J Clark was built-in in Blackpool, U.k.	Anthony Clark	Roslin Institute
1974	First publication on inserting foreign DNA into mice	Jaenisch, Mintz	Salk Establish, Trick Chase Found for Cancer Enquiry
September 1980	Scientists reported the first successful development of transgenic mice	Barbosa, Gordon, Plotkin, Ruddle, Scangos	Yale Academy
Nov 1980	Technique published using fine glass micropipettes to inject DNA directly into the nuclei of cultured mammalian cells. High efficiency of the method enables investigators to generate transgenic mice containing random insertions of exogenous DNA.	Capecchi	University of Utah
5 Nov 1981	Commencement successful transmission of foreign Deoxyribonucleic acid into laboratory mice	Constantini, Lacy	Oxford Academy, Yale University
December 1982	Behemothic mice made with the injection of rat growth hormone	Brinster, Palmiter	University of Pennsylvania, Academy of Washington Seattle
1983	Course started in the molecular embyology of mice	Costantini, Hogan, Lacy	Common cold Spring Harbour Laboratory, NIMR, Sloan Kettering Cancer Research Middle, Columbia University
1985	Offset transgenic mice created with with genes coding for both the heavy and lite concatenation domains in an antibody.	Kohler, Rusconi	Max-Planck Institute
6 Nov 1987	Publication of cistron targeting technique for targetting mutations in any cistron	Thomas, Capecchi	University of Utah
1988	Patent application filed for a method to create transgenic mice for the production of human antibodies	Bruggeman, Caskey, Neuberger, Surani, Teale, Waldmann, Williams	Laboratory of Molecular Biology, Babraham Institute, Cambridge University
12 Apr 1988	OncoMouse patent granted	Leder, Stewart	Harvard University
12 Jun 1992	First transgenic mouse model created for studying link betwixt DNA methylation and affliction	Li, Bestor, Jaenisch	Whitehead Institute for Biomedical Inquiry
1994	Outset transgenic mice strains reported for producing human monoclonal antibodies	Bruggemann, S.Green, Lonsberg, Neuberger	Cell Genesys, GenPharm, Laboratory of Molecular Biology
v Jul 1996	Dolly the sheep, the beginning cloned mammal, was born	Wilmut, Campbell	Roslin Institute
9 Jul 1997	Nascence of first sheep cloned with human being genes	Schnieke, Kind, Ritchie, Mycock, Scott, Wilmutt, Colman, Campbell	PPL Therapeutics, Roslin Plant
14 Feb 2003	Dolly the sheep, the offset cloned mammal, died	Wilmut	Roslin Constitute
12 Aug 2004	Anthony J Clark died	Anthony Clark	Roslin Institute
September 2006	First fully human monoclonal antibody drug approved		Agensys, Amgen
2007	Nobel Prize for Physiology for Medicine awarded for discoveries enabling germline cistron modification in mice using embryonic stalk cells	Capecchi, Evans, Smithies	University of North Carolina, University of Utah
x Mar 2013	Frank Ruddle died in New Haven, Connecticut	Ruddle	Yale Academy
26 Oct 2013	Michael Neuberger died	Neuberger	Laboratory of Molecular Biology
23 Sep 2015	Beijing Genomics Constitute announced the sale of the first micropigs created with the help of the TALENs gene-editing technique		Beijing Genomics Institute
five Oct 2015	CRISPR/Cas9 modified threescore genes in pig embryos in get-go step to create organs suitable for homo transplants	Church	Harvard University
x Jan 2017	Oliver Smithies died	Smithies	Academy of Washington, Academy of North Carolina
20 Apr 2017	Diabetes research using transgenic mice shows the protein P2X7R plays important role in inflammation and immune system offering new avenue for treating kidney disease	Menzies	University of Edinburgh, University Higher London, Imperial College
23 Jan 2019	CRISPR-Cas9 used to control genetic inheritance in mice	Grunwald, Gntz, Poplawski, Xu, Bier, Cooper	University of California San Diego
25 Sep 2021	First genetically engineered sus scrofa kidney successfully transplanted into a brain-dead human patient	Robert Montgomery	New York University
11 Jan 2022	First pig-to-homo heart transplant	Mohiuddin	Academy of Maryland

23 Jun 1925

Oliver Smithies was born in Halifax, United kingdom of great britain and northern ireland

1929

Jackson Memorial Laboratories established to develop inbred strains of mice to written report the genetics of cancer and other diseases

19 Aug 1929

Frank Ruddle was born in Westward New York, New Jersey

18 Sep 1951

Anthony J Clark was born in Blackpool, UK

1974

Kickoff publication on inserting strange DNA into mice

Sep 1980

Scientists reported the starting time successful evolution of transgenic mice

Nov 1980

Technique published using fine drinking glass micropipettes to inject DNA directly into the nuclei of cultured mammalian cells. High efficiency of the method enables investigators to generate transgenic mice containing random insertions of exogenous Deoxyribonucleic acid.

5 Nov 1981

Starting time successful transmission of foreign Dna into laboratory mice

December 1982

Giant mice fabricated with the injection of rat growth hormone

1983

Course started in the molecular embyology of mice

1985

First transgenic mice created with with genes coding for both the heavy and light chain domains in an antibody.

6 Nov 1987

Publication of gene targeting technique for targetting mutations in any factor

1988

Patent application filed for a method to create transgenic mice for the production of human antibodies

12 Apr 1988

OncoMouse patent granted

12 Jun 1992

First transgenic mouse model created for studying link between DNA methylation and affliction

1994

Starting time transgenic mice strains reported for producing human being monoclonal antibodies

5 Jul 1996

Dolly the sheep, the showtime cloned mammal, was built-in

9 Jul 1997

Nascency of first sheep cloned with human genes

14 Feb 2003

Dolly the sheep, the first cloned mammal, died

12 Aug 2004

Anthony J Clark died

Sep 2006

Offset fully human monoclonal antibody drug approved

2007

Nobel Prize for Physiology for Medicine awarded for discoveries enabling germline gene modification in mice using embryonic stalk cells

10 Mar 2013

Frank Ruddle died in New Oasis, Connecticut

26 October 2013

Michael Neuberger died

23 Sep 2015

Beijing Genomics Constitute announced the auction of the starting time micropigs created with the help of the TALENs cistron-editing technique

5 Oct 2015

CRISPR/Cas9 modified 60 genes in pig embryos in first pace to create organs suitable for man transplants

10 January 2017

Oliver Smithies died

20 Apr 2017

Diabetes research using transgenic mice shows the protein P2X7R plays important part in inflammation and immune organization offering new avenue for treating kidney disease

23 Jan 2019

CRISPR-Cas9 used to control genetic inheritance in mice

25 Sep 2021

First genetically engineered pig kidney successfully transplanted into a brain-dead human patient

xi Jan 2022

First squealer-to-human heart transplant

Source: https://whatisbiotechnology.org/index.php/science/summary/transgenic/transgenic-animals-have-genes-from-other-species-inserted

Posted by: johnsonhatome.blogspot.com

Share this post