Animal model

An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process. The animal chosen will usually meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed. Many drugs, treatments and cures for human diseases have been developed with the use of animal models.^[1][2] Animal models representing specific taxonomic groups in the research and study of developmental processes are also referred to as model organisms.^[2] There are three main types of animal models Homologous, Isomorphic and predictive. Homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease. Isomorphic animals share the same symptoms and treatments. This is the principle research tool. Predictive models are when the animals strictly display only the treatment characteristics of a disease. This method is commonly used when researchers do not know the cause of a disease. It is also useful in screening. ^[3]

Taxonomic human equivalence

Whereas a mouse or dog may serve as a mammalian animal model, a baboon or macaque may serve as a less inclusive primate animal model.^[4] An animal model for vertebrates is the zebrafish.^[1][2]

Danio rerio, better known as the zebrafish

Disease models

Animal models serving in research may have an existing, inbred or induced disease or injury that is similar to a human condition. These test conditions are often termed as animal models of disease. The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human.^{[citation needed]}

In order to serve as a useful model, a modeled disease must be similar in etiology (mechanism of cause) and function to the human equivalent. Animal models are used to learn more about a disease, its diagnosis and its treatment. For instance, behavioral analogues of anxiety or pain in laboratory animals can be used to screen and test new drugs for the treatment of these conditions in humans. A 2000 study found that animal models predicted human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone.^[5]

Animal models of disease can be spontaneous (naturally occurring in animals), or be induced by physical, chemical or biological means. For example,

• The use of metrazol (pentylenetetrazol) as an animal model of epilepsy^[6]
• Immunisation with an auto-antigen to induce an immune response to model autoimmune diseases such as Experimental autoimmune encephalomyelitis^[7]
• Occlusion of the middle cerebral artery as an animal model of ischemic stroke^[8]
• Injection of blood in the basal ganglia of mice as a model for stroke^[9]
• Infecting animals with pathogens to reproduce human infectious diseases
• Injecting animals with agonists or antagonists of various neurotransmitters to reproduce human mental disorders
• Using ionizing radiation to cause tumors
• Implanting animals with tumors to test and develop treatments using ionizing radiation
• Genetically selected (such as in diabetic mice also known as NOD mice)^[10]
• Various animal models for screening of drugs for the treatment of glaucoma
• The use of the ovariectomized rat in osteoporosis research
• Use of Plasmodium yoelii as a model of human malaria ^[11][12][13]

The increase in knowledge of the genomes of non-human primates and other mammals that are genetically close to humans is allowing the production of genetically engineered animal tissues, organs and even animal species which express human diseases, providing a more robust model of human diseases in an animal model.

Behavioral sciences

Animal models observed in the sciences of psychology and sociology are often termed animal models of behavior. It is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Animals lack self-consciousness, self-reflection and consideration; moreover, hallmarks of the disorder such as depressed mood, low self-esteem or suicidality are hardly accessible in non-humans. However, depression, as other mental disorders, constitutes of endophenotypes ^[14] that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular, genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and the causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into pathology of depression. In addition, animal models of depression are indispensable for identifying novel therapies for depression.^{[citation needed]}

Genetics

In quantitative genetics, the term animal model usually refers to a statistical model in which phenotypic variance is compartmentalised into environmental, genetic and sometimes maternal effects. Such animal models are also known as "mixed models".^{[citation needed]}

Criticisms

Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary, obese and glucose intolerant. This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise.^[15]

Animal models of psychiatric illness give rise to other concerns. Qualitative assessments of behavior are too often subjective, leading the investigator to observe what s/he wants to observe, and to conclude what s/he set out to conclude. Also, the imprecise diagnostic criteria for psychiatric illnesses inevitably lead to problems modeling the condition; e.g., since a person with major depressive disorder may experience weight loss or weight gain, insomnia or hypersomnia, we cannot with any certainty say that a rat with insomnia and weight loss is depressed. Furthermore, the complex nature of psychiatric conditions makes it difficult/impossible to translate human behaviors and deficits; e.g., language deficit plays a major role in autistic spectrum disorders, but - since rodents do not have language - it is not possible to develop a language-impaired "autistic" mouse.^{[citation needed]}

In addition to the myriad ethical concerns of using animals in biomedical research, animal studies of psychiatric illness raise further concerns about the pain and suffering inflicted on the test subjects. While some scientists argue that care is taken to prevent unnecessary suffering in animal experiments, suffering is an inherent aspect of modeling distressful psychiatric conditions (e.g., anxiety, depression, posttraumatic stress disorder).^{[citation needed]}

See also

• Britches (monkey)
• Animal testing
• Ensembl genome database
• In vivo
• Animal testing on invertebrates
• Animal testing on rodents
• History of animal testing
• Knockout rat
• Mouse models of colorectal and intestinal cancer

References

1. ^ ^{a b} Chakraborty C, H. C.; Hsu, C. H.; Wen, Z. H.; Lin, C. S.; Agoramoorthy, G. (Feb 2009). "Zebrafish: a complete animal model for in vivo drug discovery and development". Current Drug Metabolism 10 (2): 116–124. doi:10.2174/138920009787522197. ISSN 1389-2002. PMID 19275547.  edit
2. ^ ^{a b c} Kari, G.; Rodeck, U.; Dicker, A. P. (July 2007). "Zebrafish: an emerging model system for human disease and drug discovery". Clinical Pharmacology and Therapeutics 82 (1): 70–80. doi:10.1038/sj.clpt.6100223. ISSN 0009-9236. PMID 17495877.  edit
3. ^ http://academic.uprm.edu/~ephoebus/id85.htm
4. ^ Shively, C. A.; Clarkson, T. B. (June 2009). "The unique value of primate models in translational research". American Journal of Primatology 71 (9): 715–721. doi:10.1002/ajp.20720. ISSN 0275-2565. PMID 19507247.  edit
5. ^ Olson H, Betton G, Robinson D, et al. (August 2000). "Concordance of the toxicity of pharmaceuticals in humans and in animals". Regul. Toxicol. Pharmacol. 32 (1): 56–67. doi:10.1006/rtph.2000.1399. PMID 11029269. 
6. ^ White HS (1997). "Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs". Epilepsia 38 Suppl 1: S9–17. doi:10.1111/j.1528-1157.1997.tb04523.x. PMID 9092952. 
7. ^ Bolton C (2007). "The translation of drug efficacy from in vivo models to human disease with special reference to experimental autoimmune encephalomyelitis and multiple sclerosis". Inflammopharmacology 15 (5): 183–7. doi:10.1007/s10787-007-1607-z. PMID 17943249. 
8. ^ Leker RR, Constantini S (2002). "Experimental models in focal cerebral ischemia: are we there yet?". Acta Neurochir. Suppl. 83: 55–9. PMID 12442622. 
9. ^ Rynkowski MA, Kim GH, Komotar RJ, et al. (2008). "A mouse model of intracerebral hemorrhage using autologous blood infusion". Nat Protoc 3 (1): 122–8. doi:10.1038/nprot.2007.513. PMID 18193028. 
10. ^ Homo-Delarche F, Drexhage HA (2004). "Immune cells, pancreas development, regeneration and type 1 diabetes". Trends Immunol. 25 (5): 222–9. doi:10.1016/j.it.2004.02.012. PMID 15099561. 
11. ^ Hisaeda H, Maekawa Y, Iwakawa D, et al. (2004). "Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells". Nat. Med. 10 (1): 29–30. doi:10.1038/nm975. PMID 14702631. 
12. ^ Coppi A, Cabinian M, Mirelman D, Sinnis P (2006). "Antimalarial activity of allicin, a biologically active compound from garlic cloves". Antimicrob. Agents Chemother. 50 (5): 1731–7. doi:10.1128/AAC.50.5.1731-1737.2006. PMC 1472199. PMID 16641443. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1472199. 
13. ^ Frischknecht F, Martin B, Thiery I, Bourgouin C, Menard R (2006). "Using green fluorescent malaria parasites to screen for permissive vector mosquitoes". Malar. J. 5: 23. doi:10.1186/1475-2875-5-23. PMC 1450296. PMID 16569221. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1450296. 
14. ^ Hasler, G. et al. (2004) Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 1765–1781
15. ^ Martin B, Ji S, Maudsley S, Mattson MP (2010). ""Control" laboratory rodents are metabolically morbid: Why it matters.". Proc Natl Acad Sci U S A 107 (14): 6127–6133. doi:10.1073/pnas.0912955107. PMC 2852022. PMID 20194732. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2852022. 

External links

• Disease Animal Models - BSRC Alexander Fleming
• Transgenic Animal Models - Biomedcode
• Knock Out Rat Consortium - KORC
• Emice - National Cancer Institute