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knockout mouse

Knockout Mouse
1. Introduction
Generally, DNA was first transferred by design into an organism and expressed as protein, therefore the potential of the tool that was being discovered must be found quickly by the scientist. Early experiments were limited to bacteria and viruses, but soon after the field of experiments were enlarged to those on animals and plants. (E.Hill, 2002).
This topic, “knockout mouse” relates to the field of genetic engineering which further delves into a more specific technique called transgenic technology. “Knockoutscience.com”(2009) analyses that transgenic technology refers to the alteration of a certain genomic DNA of an organism in genetic engineering. As the result, both offspring of a transgenic organism and the parents (homozygous) will share the same genotype. The most common type of transgenic organism used in research is the knockout mouse, thoughknockout rats andknockout rabbits have also been developed.
A knockout mouse defines a mouse which is being genetically engineered by turning off one or more genes through a process called gene knockout. “Genome.gov “also explains that a knockout mouse is a laboratory mouse in which researchers have inactivated, an existing gene by replacing it or disrupting it with an simulated piece of DNA. The loss of gene activity often causes changes in a mouse’s phenotype, which includes appearance, activities and other observable physical and biochemical characters.
“Knockoutscience.com” (2009) also elucidates that it has become routine to develop knockout mice with disruptions in specific genes. By observing the resulting phenotype, scientists are able to view the effects of this gene disruption from these knockout mice. It is true to say that the phenotype is a direct result of the gene knockout and can offer evidences as to the biological role of the gene, but rarely the phenotype can also be the result of compensatory or indirect effects of the gene knockout. Sometimes the result obtained in a phenotype can be completely unrelated to the disrupted gene. Additionally, some gene knockouts create alethal phenotypewhere the organism fails to develop in utero, making in vivo studies exceedingly difficult.
It was claimed that this technique may help to solve dopamine-related neurological illnesses.(Carol A.T, 1996) The technique allows transgenic animals that lack of a certain gene or its associated protein product to grow. In experiments with mice, researchers were able to knockout the animals’ dopamine transporters, causing the mice to behave as if they had been given huge doses of cocaine or amphetamine.
Walinski.H(2009) states that knockout mice have different way of uses. First, the specific functions of particular genes can be tested and the regulation of these particular genes can be observed. The effects of a particular gene can be determined by examining what is happening in anin vivo model, we are able to determine the effects a particular gene may have. These effects would be impossible to observe in a culture dish.
Another useful application of knockout technology is in biomedical research and drug development. Knockout mouse can be used to study the evolution of thousands of genetically based diseases at the molecular level in order to seek for the best medications that act on that gene. For Example, Lili.X and Asok.C (2005 ) both agree that Duffy positive and Duffy knockout mice have revealed both human malaria parasite Plasmodium vivax and mouse malaria parasite Plasmodium yoelii by using parasite invasion. Furthermore, the knockout technology may lead to the discovery of the next generation of blockbuster therapies for curing numerous diseases based on novel targets from the human genome.
2. Background Genetics
Timeline for the key events in the history of knockout mouse
1900 – Japanese fancy mice became mutant resources for mouse genetics.
1915- The first verterbrate linkage (mapping) was discovered between albino (c) and pink-eyed dilution (p) loci in the mouse.
1923- Discovery of X-ray induced mutations in mouse before the phenomenon was confirmed in fruit-flies.
1980- Specific-locus tests were conducted extensively in the mouse with various chemical mutagens, including N-ethyl-N-nitrosourea (ENU).
1981-1991- knockout mice are established.
1981- The first embryo stem (ES) cell was identified in the mouse. Martin Evans and Matt Kaufman in Cambridge, U.K., isolate mouse embryonic stem cells, which can develop into the full range of tissues.
1982-Transgenic mouse technology was established through the generation of the “giant mouse” mutant.
1985- Introduction of the Cre-loxP system by Brian Sauer act as temporal control of transgenic gene expression.
1987- Mario Capecchi’s team at the University of Utah describes a method for making knockout mice, as does Oliver Smithies’s group at the University of Wisconsin.
1989- First knockout mouse was made by combining ES cell and gene-targeting technologies.
2007- International Knockout Mouse Consortium was organized and the Banbury II meeting was held in Brussels, Belgium. Nobel Prize for Physiology and Medicine was awarded for the development of mouse knockout techonologies.
3. Genetic Technique
There are several method to produce knockout mouse, such as gene deletion, homologous recombination method, pronuclear microinjection and gene targeting. However, only gene targeting will be mentioned herein.
Gene Targeting is the elimination or alteration of a gene’s function. One of the advantages of gene targeting is a mutant allele can be mended by substituting a wild-type allele over the mutant one in its normal chromosomal location, and such technique known as gene replacement. In this way, both position effect and the DNA rearrangements associated with ectopic insertion can be prevented, as a single replication of the gene is inserted in its normal chromosomal environmental. (Griffiths.A and Susan R.Wessler,etc, 2008).
4. Social Issues
Recently, the evaluation of animal and human welfare as it may be affected by biotechnology is becoming a hot issue. The lack of an conscience and the information of the processes involved is one of the most important fact. ( Marie.B, 1997)
Marie.B (1997) also states that the moral evaluation process is complicated by the fact that many techniques and developments in biotechnology are appropriate for patent. Some of the biotechnologists are reluctant to reveal appropriate information is understandable.
Therefore, education concerning transgenic animal care and utilize is indeed very importance, involving the careful consideration of the reasons for manipulating the genome of any organism as genetic engineering is a dangerous and sensitive social issue. ( Marie.B, 1997)
Pros and Cons of Knockout Mouse
Advantages
Disadvantages
Provides important clues about what that gene normally does because human share many genes with mice. (Genome.gov, 2009)
Limitation of the utility of knockout mice as models of human disease. (Walinski.H, 2004)
Gives better understanding and observation of the characteristics of knockout mice. ( Genome.gov, 2009)
The lack of adult mice limits studies to embryonic development and makes it more difficult to determine a gene’s function in relation to human health. ( Genome.gov, 2009)
Gives information that can be used to better understand how a similar gene may cause or contribute disease in human. ( Genome, 2009)
The gene that being examined might serve a different function in adults than in developing embryos, giving a false information. (Genome, 2009)
Useful in studying and modeling different kinds of cancer, obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease.
Fails to produce an observable change in a mouse or may even produce a different characteristics from those observed in humans in which the same gene is inactivated. ( Genome.gov, 2009) Offers a biological context in which drugs and other therapies can be developed and tested.
Producing custom knockout mice is very expensive. It can be from 3000 to as much as 30,000 (Walinski.H, 2004)
Useful in drug development and helps to discover the next generation of blockbuster therapies for curing numerous diseases based on novel targets from the humane genome. (Walinski.H, 2004)
The cost of equipping and maintaining such a facility is usually very high. ( Walinski.H, 2009)
5.0: Conclusion
In conclusion, it is clear that knockout mouse offer a lot of benefits for us. Therefore, a thorough discussion of biotechnology issues is needed, as concurrence must be practiced as to protect transgenic animals. The field of transgenic animal biotechnology is likely to rise as the techniques develop further and will link to more applications by using many more animal species. Thus, it is important that the welfare and ethical concerns must continue to evolve. (Marie.B, 1997) In short, technology essentials together with thoughtful ethical decision-making are equally important to maintain the balance of living creatures.
6.0: Bibliography
* Connor A.B, 2007, Schematic and Time Line for the Generation of Knockout Mice, Viewed 25 January 2010, http://web.mit.edu/ki/facilities/transgenic/services/timeline-complete.pdf
* Davidson, NC 28036, Homologous Recombination

The Lamentation over the Dead Christ

Classicism in “The Lamentation over the Dead Christ”
The Renaissance Era was an epoch of artistic resurgence in the history of Europe. This period was marked by developments in Italian Renaissance paintings with the renewal of classical forms, motifs and subjects. In edict to discern the Classicism that prospered during this age, conceivably without need, from the Classical architecture of the ancient Romans. The exploration for cerebral legitimacy through art set apart the period. During this period, contemporary Classicism was described as the “proper technique”. Methodically, this set in motion a blitz against Baroque art, which, with its highlighting of embellishment and delusion, was considered to be distinctly fictitious. Andrea Mantegna (1431-1506), in particular, modeled his work entitled “The Lamentation over the Dead Christ” (c.1480) in rudiments of Classicism.
Mantegna used mainly foreshortening, a perspective used for compressing objects from a definitive viewpoint and chiaroscuro, the contrast between light and shadows bring this painting to life with essentials of Classicism. In this period, Classicism took on more visibly structural insinuations of the use of perspective, chiefly by the use of Foreshortening. Foreshortening occurs when an object appears compressed when seen from a particular viewpoint, and the effect of perspective causes distortion.
Foreshortening is a predominantly constructive creative mechanism, used to give the sense of three-dimensional capacity and generate emotion in a picture. To sensationalize the supine Christ in perception, Mantegna paints his light source higher up the horizon line, to create illusion that the viewer will appear to be looking at an angle. The more askew the vanishing point, the more slanted the icon will be, as seen in the painting. Because the body of Christ is supine and symmetrical, the vanishing point is diametrically in the core of the perspective line. Because the spectator’s plane is parallel to Christ’s head at this point, the base perspective line appears to be horizontal. This imaginary line gives the fundamental, “foreshortening” perspective. The farther away the image is from the viewer, the nearer the illusion is to being perpendicular to the portrait plane, as seen in the Dead Christ. The position of the mourners (The Virgin Mary and St. John) are on the horizon line, to the left the desertion point (Christ’s Head), as another foremost model to carry this position of foreshortening. The expanse from this point to the center of the perspective line denotes the distance within the painting for the viewer. If the point is isolated from the vanishing point, the mourners will appear condensed, and distant. If it is too close, they will emerge lengthened, as if it is too close to the observer. Essentially distorting the ray of light traveling from it’s origin to the onlooker’s judgment and ruining the illusion within the painting. This element is key to understanding Mantegna’s brilliance of perspective in this fresco. In the case of the holes in Christ’s hands and feet; the perspective of the light source that illuminates (at an angle) the area of the holes also represents the use of foreshortening on the picture plane. When the light source hits the area of the holes, it hits at the appropriate angle on the picture plane. In order for the resulting image to appear identical to the intended scene, the eyewitness of the perspective must scrutinize the image from the exact vantage point used in the geometric calculations comparative to Christ. This proper use of foreshortening abandons visual imperfections that what would appear to be alterations in the painting when analyzed from a discrete point. These conspicuous distortions in foreshortening are more evident when viewing Christ’s thorax; as the perspective estimated from the surroundings, to the spectator becomes more finely tuned and comparative to the portrait base.
In application, unless the viewer desires a radical perspective, like viewing the body of Christ from the base, the perspective on the whole, is in all probability accurate. It has been recommended that a painting in standpoint still seems to be in perspective at other spots because the individual still distinguishes it as a painting, because of the quality in its profundity of field indications due to the use of foreshortening. For a emblematic perspective, conversely, the field of view in the Dead Christ is tapered to the point, that the distortions are negligible and the fresco can be viewed from a site other than the tangible designed vantage point without seeming distorted, which in turn, buttress’ Mantegna’s conclusion to paint the feet of Christ less significant than the customary individuals. While speaking at a summit on Greek mathematics and philosophy, Plato (429-347 B.C.E.) was quoted in repute to artwork, as stating,
Thus (through perspective) every sort of confusion is revealed within us; and this is that weakness of the human mind on which the art of conjuring and of deceiving by light and shadow and other ingenious devices imposes, having an effect upon us like magic… And the arts of measuring and numbering and weighing come to the rescue of the human understanding… (Plato qtd. in Kahn)
The applied use of the expression “chiaroscuro”, is the outcome of light representation in painting, in which three- dimensional capacity is advocated by the measure of color and the systematic partition of light and shadow contours on a two dimensional plane in a model of artwork. The creation of these belongings in the West, Skiagraphia or “shadow-painting” to the primeval Greeks, was attributed to the celebrated Athenian painter of the 5th century BC, Apollodoros. In the print of the Dead Christ, the light is approaching in from one encoded course exceeding Christ’s body, then light and silhouette will match to a set of natural conventions. An underscore of luminosity on Christ’s shroud symbolizes the summit where the brilliance is being revealed most unswervingly. This is most often attributed as a lightened white area, as seen in the shroud in Figure 1. As the viewer’s eye moves away from this emphasis, radiance strikes the article less candidly and consequently broadcasts a darker assessment of hues on the shroud. This changeover continues until the onlooker reaches the point where the darkness of the piercingly drawn material meets the lighted portion of the shroud. Here, there is a more abrupt conversion to darker values since no light is salient between Christ’s feet. Some oblique light is offered on the underside of Christ’s feet as the muted side does not turn unyieldingly dark. This is the product of reflected and refracted daylight that logically become apparent within the painting. As the viewer looks at the intense frame of the body of Christ, it is noticeable that it is patently lighter than the shadowed area of the mourners. Light in the environment is illuminating the background. The throw shadows are at odds, with separate values as well. Then, as light becomes more available, the same cast shadow lightens in increments until it reaches the shadow’s circumference. Craigie Aitchison (1923-2009), a Scottish painter and one of the better known critically esteemed Royal Academians (Members Royal Academy of Arts have a exclusive position in being recognized as reputed artists and architects whose sole objective is to endorse the creation, pleasure and awarnessof the visual arts through exhibitions, education and debate), recalls the Dead Christ as his favorite painting, stating, “I like it because it tells a Story… It’s a wonderful reddy colour and terrifically drawn… “If ever a painting was clear, it’s this one. It’s fantastically clear about the story it’s telling – there’s no muddling about. It couldn’t be any other way.”” (Aitchison). Mantegna dominates and operates this modus operandi to generate a inventive sense of pathos in the mourners and character in the Dead Christ. The Mantegna painting, with light entering from above, illustrates a faint modeling of chiaroscuro to give quantity to the body of Christ, which in turn, confirms the strong stimulus of Greek inspired Classicism in this fresco. The contrasts between light and shadows bring this painting to life with essentials of Classicism.
The Renaissance Era was an epoch of artistic resurgence in the history of Europe. This period was marked by developments in Italian Renaissance paintings with the renewal of classical forms, motifs and subjects. In edict to discern the Classicism that prospered during this age, conceivably without need, from the Classical architecture of the ancient Romans. The exploration for cerebral legitimacy through art set apart the period. During this period, contemporary Classicism was described as the “proper technique”. Methodically, this set in motion a blitz against Baroque art, which, with its highlighting of embellishment and delusion, was considered to be distinctly fictitious. Andrea Mantegna (1431-1506), in particular, modeled his work entitled “The Lamentation over the Dead Christ” (c.1480) in rudiments of Classicism.
Mantegna used mainly foreshortening, a perspective used for compressing objects from a definitive viewpoint and chiaroscuro, the contrast between light and shadows bring this painting to life with essentials of Classicism. Mantegna’s version of the Dead Christ, is regarded as an indispensable art piece exemplifying the use of Classicism. Thus, he deserves the acclaim for the merit of these essentials in his work of art.

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