Which Of The Following Statements Is Incorrect About Transgenic Animals

Transgenic animals

Definition

A transgenic animal is one whose genome has been altered by the transfer of a cistron or genes from another species or breed.

The photo shows two transgenic mice positioned either side of a plain mouse. The transgenic mice take been genetically modified and so that they conduct a dark-green fluorescent protein which glows green nether blue calorie-free. Credit: Ingrid Moen et alet al., BMC Cancer, 12/21 (2012), 1-10.

Importance

Transgenic animals are routinely used in the laboratory as models in biomedical enquiry. Over 95 per cent of those used are genetically modified rodents, predominantly mice. They are important tools for researching homo affliction, being used to understand factor function in the context of illness susceptibility, progression and to determine responses to a therapeutic intervention.

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

Transgenic subcontract animals are too being 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 procedure is expensive. In 2008, for example, the building of a new prison cell-based manufacturing facility for i therapeutic protein was estimated to cost over Us$500 meg. A cheaper choice would exist to develop a ways to produce recombinant proteins in the milk, blood or eggs of transgenic animals. Progress in this area, all the same, has been slow to-date. Merely two biomedical products have so far received regulatory blessing. The commencement is man antithrombin III, a therapeutic protein produced in the milk of transgenic goats, which is used to prevent clots in patients with hereditary antithrombin deficiency receiving surgery or undergoing childbirth. A relatively minor herd of goats (almost 80) can supply enough man antithrombin III for all of Europe. The second product is a recombinant human 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 claret to expand and crusade 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 first successful transfer of embryos was accomplished past Walter Heape in Angora rabbits in 1891. Some other important component is the ability to manipulate the embryo. In vitro manipulation of embryos in mice was get-go reported in the 1940s using a civilisation arrangement. What is too vital is the ability to manipulate eggs. This was made possible through the efforts of Ralph Brinster, attached to the Academy of Pennsylvania, who in 1963 devised a reliable system to culture eggs, and that of Teh Ping Lin, based at the California Schoolhouse of Medicine, who in 1966 outlined a technique to micro-inject fertilised mouse eggs which enabled the accurate insertion of foreign Dna.

The commencement genetic modification of animals was reported in 1974 by the virologist Rudolph Jaenisch, so at the Salk Institute, and the mouse embryologist Beatrice Mintz at Fox Hunt Cancer Heart. They demonstrated the feasibility of modifying genes in mice by injecting the SV40 virus into early-phase mouse embryos. The resulting mice carried the modified gene in all their tissues. In 1976, Jaenisch reported that the Moloney Murine Leukemia Virus could also exist passed on to offspring by infecting an embryo. Four years later, in 1980, Jon Gordon and George Scango together with Frank Ruddle, announced the nativity of a mouse built-in with genetic material they had inserted into newly fertilised mouse eggs. Past 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 Fox Chase Cancer Center 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 as a laboratory tool to amend sympathize the onset and progression of cancer. The advantage of such mice is that they provide a model which closely mimics the human body. The mice not just provide a means to gain greater insight into cancer but too to test experimental drugs.

Application

Transgenic animals are animals (most normally mice) that have had a foreign gene deliberately inserted into their genome. Such animals are most commonly created past the microinjection of Dna into the pronuclei of a fertilised egg which is after implanted into the oviduct of a pseudopregnant surrogate mother. This results in the recipient animal giving birth to genetically modified offspring. The progeny are then bred with other transgenic offspring to establish a transgenic line. Transgenic animals can too be created past inserting Dna into embryonic stem cells which are and then micro-injected into an embryo which has developed for five or vi days later on fertilisation, or infecting an embryo with viruses that bear a DNA of involvement. This final method is commonly used to manipulate a single factor, in most cases this involves removing or 'knocking out' a target gene. The end result is what is known every bit a 'knockout' animal.

Since the mid-1980s transgenic mice accept get a cardinal model for investigating disease. Mice are the model of choice non only considering there is extensive analysis of its completed genome sequence, but its genome is similar to the homo. Moreover, physiologic and behavioural tests performed on mice can be extrapolated directly to human disease. Robust and sophisticated techniques are also easily available for the generic manipulation of mouse cells and embryos. Another advantage of mice is the fact that they have a short reproduction cycle. Other transgenic species, such as hog, sheep and rats are too used, only their employ in pharmaceutical inquiry has so far been limited due to technical constraints. Recent technological advances, however, are laying the foundation for wider adoption of the transgenic rat.

Transgenic rodents play a number of critical roles in drug discovery and development. Chiefly, 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 affliction biological science and facilitated the identification of new drug targets. Due to their similarity in physiology and gene role between humans and rodents, transgenic rodents can be developed to mimic human being affliction. Indeed, an array of transgenic mice models have been produced for this purpose. Mice are being used every bit models, for example, to written report obesity, heart illness, diabetes, arthritis, substance corruption, anxiety, ageing, Alzheimer'due south disease and Parkinson's disease. They are besides used to study unlike forms of cancer. In addition, transgenic pigs are being investigated every bit a source of organs for transplants, which if proven clinically safe could overcome some of the severe donor organ shortages. The development of transgenic animals has recently been transformed by the emergence of the new gene editing tool CRISPR which greatly reduced the number of steps involved in the creation of transgenic animals, making the whole process much faster and less costly.

This section on transgenic mice was jointly written by Lara Marks and Dmitriy Myelnikov. For more information see D. Myelnikov, 'Transforming mice: technique and advice in the making of transgenic animals, 1974-1988', unpublished PhD, Cambridge University, 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 study human protein variation. Later on, in the 1980s he developed a method for targeted factor 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 conveying desired genetic mutations. Such mice are at present widely used to investigate the part of many different genes in human being wellness and disease. 1925-06-23T00:00:00+0000 Founded by Clarence Lilliputian, i of the leading researchers into genetic differences governing the rejection of strange 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 Man Genome Project. He generated, with Jon W. Gordon and George Scango the first successful transgenic mouse. This heralded the evolution of genetically modified animals every bit research models to investigate the role of genes and genetic crusade of disease. Ruddle too discovered, with William McGinnis, the first homo homeobox genes, important regulators of gene development. 1929-08-19T00:00:00+0000 Clark was a molecular biologist who used genetic engineering 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 large 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 Deoxyribonucleic acid engineering. 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 One thousand Capecchi, 'High efficiency transformation by 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 cistron to be after transmitted into the offspring. This was the offset pace towards the development of transgenic mice. F Costantini, E Lacy, 'Introduction of a rabbit b-globin gene into the mouse germ line', Nature, 294 (1981), 92–4. 1981-11-05T00:00:00+0000 1982-12-01T00:00:00+0000 The course is started at Common 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 stalk cells', Jail cell, 51/3 (1987), 503-12. 1987-11-06T00:00:00+0000 This patent is filed on the basis of work reported in 1000 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 iv,736,866 awarded for transgenic mouse with activated oncogenes created by 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 enquiry and the testing of new drugs. Information technology was the first fauna ever given patent protection in the USA. 1988-04-12T00:00:00+0000 Mouse genetated with genes knocked out that produce the enzyme Dna methyltransfgerase involved in DNA methylation. E. Li, T.H. Bestor, R. Jaenisch, 'Targeted mutation of the DNA methyltransferase factor results in embryonic lethality', Prison cell, 69/vi (1992), 915-26. 1992-06-12T00:00:00+0000 Three groups of scientists separately report the successful generation of different strains of transgenic mice for the generation of human being monoclonal antibodies. 2 of the teams are based in biotechnology companies: GenPharm (led past Nils Lonsberg), Prison cell Gensys (led by Larry Green) , and the other involved a collaboration (led past Marian Bruggemann and Michael Neuberger) between scientists at the Laboratory of Molecular Biology, Braham Found and the University of Cologne. 1994-01-01T00:00:00+0000 Dolly the sheep was created by cloning an adult prison cell. This was done by transferring the nucleus of an adult sheep's cell to the nucleus of an unfertilised egg cell. It took 277 attempts to attain success. The work was carried out by 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 1 of six cloned lambs which had human being genes inserted. The cistron that was transferred was linked to then human being blood clotting factor 9. Such genetic technology was done to demonstrate the potential of such recombinant DNA applied science combined with animal cloning. Information technology was done in the promise that 1 day transgenic animals might provide pharmacological and therapeutic proteins and transplant organs to treat human diseases. The piece of work was published in AE Schnieke; et al, 'Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts', Science, 278/5346 (1997), 2130–33. 1997-07-09T00:00:00+0000 Dolly the sheep was created by cloning an adult cell. This was done by transferring the nucleus of an adult sheep's prison cell to the nucleus of an unfertilised egg prison cell. It took 277 attempts to attain success. 2003-02-14T00:00:00+0000 Clark was a British molecular biologist who used genetic applied science to create the outset sheep capable of producing big quantities of man poly peptide. The sheep, Tracy, built-in in 1990, provided 35g of the alpha-ane-antitrypsin in each litre of her milk. The protein is used in the treatment of cystic fibrosis. Clark likewise 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 canonical past the FDA for the treatment of patients with EGFR-expressing metatastic colorectal cancer. The drug is a fully man monoclonal antibiotic created with transgenic mice. It was developed by Agensys with Amgen. 2006-09-27T00:00:00+0000 The Prize was awarded to to Mario Capecchi, Martin Evans and Oliver Smithies. Their work made it possible to modify specoific genes in the germline of mammals which could produce offspring that carried and expressed the modified gene. Their method is usually 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 man gene mapping and established many of the techniques and a framework for setting up the Human Genome Project. He likewise generated, with Jon W. Gordon and George Scango the starting time successful transgenic mouse. This heralded the development of genetically modified animals as research models to investigate the office of genes and genetic cause of disease. Ruddle also discovered, with William McGinnis, the first man homeobox genes, important regulators of gene development. 2013-03-10T00:00:00+0000 A pioneer of antibody technology, Neuberger adult some of the first techniques for the generation of chimeric and humanised antibodies. He likewise helped create the offset transgenic mice for the production of human monoclonal antibodies. His piece of work paved the way for the generation of safer and more than constructive monoclonal antibody drugs. 2013-10-26T00:00:00+0000 The pigs, a pocket-size breed known as Bama, had some of their genes disabled. They were adult for employ in studying stem cells, gut microbiota, and Laron syndome, a type of dwarfism caused by a mutation in the homo GHR gene. The announcement was fabricated at Shenzhen International Biotech Leaders Pinnacle. 2015-09-23T00:00:00+0000 The aim was to to inactivate 62 endogenous retroviruses in the pig embryos. All pigs have these viruses embedded in their genomes. The presence of such viruses, which tin can transmit diseases like cancer, is a major hurdle to the transplant of pig organs into humans. The cistron editing work was carried out by the geneticist George Church of Harvard Medical Schoolhouse. He and his squad 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 start made his mark in 1955 through his invention of starch gel electrophoresis, a technique used to study human poly peptide variation. Subsequently, in the 1980s he adult a method for targeted cistron 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 conveying desired genetic mutations. Such mice are now widely used to investigate the role of many unlike genes in homo 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 bulldoze, called a cassette, which encoded a guide RNA that targets a sequence in the TYR gene which affects the mouse coat 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 by CRISPR–Cas9 in the female mouse germline', Nature, Jan 23, 2019. 2019-01-23T00:00:00+0000 A squad of surgeons led by Robert Montgomery at New York University Langone Health fastened the organ to a brain-expressionless individual who was being maintained on a ventilator. Although the kidney remained outside the body, it worked ordinarily, making urine and creatinine, a waste matter product. 2021-09-25T00:00:00+0000 The transplant was performed on David Bennett, a 57 twelvemonth old, by doctors at the Academy of Maryland Medical Centre. The heart was taken from a squealer that had been genetically modified to knock out several genes that would accept led to the organ beingness rejected by Mr Bennett's immune system. The treatment was considered the terminal promise for saving Mr Bennett who had heart failure. Mr Bennett was reported to exist doing well three days after the operation but 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	Academy of Washington, University of N Carolina
1929	Jackson Memorial Laboratories established to develop inbred strains of mice to study the genetics of cancer and other diseases		Jackson Memorial Laboratoroies
19 Aug 1929	Frank Ruddle was born in West New York, New Jersey	Ruddle	Yale University
18 Sep 1951	Anthony J Clark was built-in in Blackpool, UK	Anthony Clark	Roslin Found
1974	Kickoff publication on inserting foreign Dna into mice	Jaenisch, Mintz	Salk Institute, Fox Hunt Institute for Cancer Research
September 1980	Scientists reported the first successful development of transgenic mice	Barbosa, Gordon, Plotkin, Ruddle, Scangos	Yale Academy
November 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	First successful manual of foreign Dna into laboratory mice	Constantini, Lacy	Oxford University, Yale University
Dec 1982	Behemothic mice made with the injection of rat growth hormone	Brinster, Palmiter	University of Pennsylvania, University of Washington Seattle
1983	Course started in the molecular embyology of mice	Costantini, Hogan, Lacy	Cold Spring Harbour Laboratory, NIMR, Sloan Kettering Cancer Research Center, Columbia University
1985	First transgenic mice created with with genes coding for both the heavy and lite concatenation domains in an antibiotic.	Kohler, Rusconi	Max-Planck Institute
6 Nov 1987	Publication of gene targeting technique for targetting mutations in any gene	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 between Dna methylation and disease	Li, Bestor, Jaenisch	Whitehead Found for Biomedical Research
1994	First 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 first cloned mammal, was built-in	Wilmut, Campbell	Roslin Institute
9 Jul 1997	Birth of showtime sheep cloned with homo genes	Schnieke, Kind, Ritchie, Mycock, Scott, Wilmutt, Colman, Campbell	PPL Therapeutics, Roslin Institute
14 February 2003	Dolly the sheep, the first cloned mammal, died	Wilmut	Roslin Institute
12 Aug 2004	Anthony J Clark died	Anthony Clark	Roslin Establish
September 2006	First fully human being monoclonal antibiotic drug approved		Agensys, Amgen
2007	Nobel Prize for Physiology for Medicine awarded for discoveries enabling germline factor modification in mice using embryonic stalk cells	Capecchi, Evans, Smithies	University of Northward Carolina, University of Utah
10 Mar 2013	Frank Ruddle died in New Haven, Connecticut	Ruddle	Yale University
26 Oct 2013	Michael Neuberger died	Neuberger	Laboratory of Molecular Biology
23 Sep 2015	Beijing Genomics Plant announced the sale of the first micropigs created with the aid of the TALENs gene-editing technique		Beijing Genomics Institute
v Oct 2015	CRISPR/Cas9 modified threescore genes in hog embryos in beginning pace to create organs suitable for human transplants	Church	Harvard University
10 January 2017	Oliver Smithies died	Smithies	Academy of Washington, University of North Carolina
20 Apr 2017	Diabetes research using transgenic mice shows the protein P2X7R plays important role in inflammation and immune organization offering new avenue for treating kidney affliction	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 pig kidney successfully transplanted into a brain-dead man patient	Robert Montgomery	New York University
11 Jan 2022	First pig-to-human middle transplant	Mohiuddin	University of Maryland

23 Jun 1925

Oliver Smithies was born in Halifax, Great britain

1929

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

19 Aug 1929

Frank Ruddle was built-in in West New York, New Jersey

18 Sep 1951

Anthony J Clark was born in Blackpool, UK

1974

First publication on inserting foreign DNA into mice

Sep 1980

Scientists reported the first successful evolution of transgenic mice

November 1980

Technique published using fine glass micropipettes to inject Deoxyribonucleic acid direct 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 November 1981

First successful manual of foreign DNA into laboratory mice

Dec 1982

Giant mice made with the injection of rat growth hormone

1983

Form started in the molecular embyology of mice

1985

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

half-dozen Nov 1987

Publication of gene targeting technique for targetting mutations in any gene

1988

Patent awarding filed for a method to create transgenic mice for the production of homo antibodies

12 Apr 1988

OncoMouse patent granted

12 Jun 1992

Beginning transgenic mouse model created for studying link between Dna methylation and affliction

1994

First transgenic mice strains reported for producing human monoclonal antibodies

5 Jul 1996

Dolly the sheep, the first cloned mammal, was born

nine Jul 1997

Nativity of first sheep cloned with human genes

14 Feb 2003

Dolly the sheep, the kickoff cloned mammal, died

12 Aug 2004

Anthony J Clark died

Sep 2006

First fully homo monoclonal antibody drug approved

2007

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

10 Mar 2013

Frank Ruddle died in New Haven, Connecticut

26 Oct 2013

Michael Neuberger died

23 Sep 2015

Beijing Genomics Institute announced the auction of the first micropigs created with the aid of the TALENs gene-editing technique

5 Oct 2015

CRISPR/Cas9 modified 60 genes in squealer embryos in commencement step to create organs suitable for human transplants

10 Jan 2017

Oliver Smithies died

20 April 2017

Diabetes research using transgenic mice shows the poly peptide P2X7R plays important office in inflammation and allowed arrangement offering new avenue for treating kidney affliction

23 Jan 2019

CRISPR-Cas9 used to command genetic inheritance in mice

25 Sep 2021

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

eleven Jan 2022

Start pig-to-human center transplant

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

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