Editing Model organism (section)

==Disease models==
{{main|Animal disease model}}
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.{{cn|date=March 2025}}

The best models of disease are similar in [[etiology]] (mechanism of cause) and phenotype (signs and symptoms) to the human equivalent. However complex human diseases can often be better understood in a simplified system in which individual parts of the disease process are isolated and examined. For instance, behavioral analogues of [[anxiety (mood)|anxiety]] or [[pain]] in laboratory animals can be used to screen and test new [[medication|drugs]] for the treatment of these conditions in humans. A 2000 study found that animal models concorded (coincided on true positives and false negatives) with human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone.<ref>{{cite journal |last1=Olson |first1=Harry |last2=Betton |first2=Graham |last3=Robinson |first3=Denise |last4=Thomas |first4=Karluss |last5=Monro |first5=Alastair |last6=Kolaja |first6=Gerald |last7=Lilly |first7=Patrick |last8=Sanders |first8=James |last9=Sipes |first9=Glenn |last10=Bracken |first10=William |last11=Dorato |first11=Michael |last12=Van Deun |first12=Koen |last13=Smith |first13=Peter |last14=Berger |first14=Bruce |last15=Heller |first15=Allen |title=Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals |journal=Regulatory Toxicology and Pharmacology |date=August 2000 |volume=32 |issue=1 |pages=56–67 |doi=10.1006/rtph.2000.1399 |pmid=11029269 }}</ref>

In 1987, Davidson et al. suggested that selection of an animal model for research be based on nine considerations. These include {{blockquote| 1) appropriateness as an analog, 2) transferability of information, 3) genetic uniformity of organisms, where applicable, 4) background knowledge of biological properties, 5) cost and availability, 6) generalizability of the results, 7) ease of and adaptability to experimental manipulation, 8) ecological consequences, and 9) ethical implications.<ref>{{Cite journal
| last1 = Davidson | first1 = M. K.
| last2 = Lindsey | first2 = J. R.
| last3 = Davis | first3 = J. K.
| title = Requirements and selection of an animal model
| journal = Israel Journal of Medical Sciences
| volume = 23
| issue = 6
| pages = 551–555
| year = 1987
| pmid = 3312096
}}</ref>}}

Animal models can be classified as homologous, isomorphic or predictive. Animal models can also be more broadly classified into four categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan.<ref name="pmid750165">{{Cite journal
| last1 = Hughes | first1 = H. C.
| last2 = Lang | first2 = C.
| doi = 10.3109/15563657808988266
| title = Basic Principles in Selecting Animal Species for Research Projects
| journal = Clinical Toxicology
| volume = 13
| issue = 5
| pages = 611–621
| year = 1978
| pmid = 750165
}}</ref>

Experimental models are most common. These refer to models of disease that resemble human conditions in phenotype or response to treatment but are induced artificially in the laboratory. Some examples include:
* The use of [[metrazol]] (pentylenetetrazol) as an animal model of [[epilepsy]]<ref name="pmid9092952">{{cite journal | author=White HS | title=Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs | journal=Epilepsia | volume=38 Suppl 1 | issue= s1 | pages=S9–17 | year=1997 | pmid=9092952 | doi=10.1111/j.1528-1157.1997.tb04523.x | doi-access=free }}</ref>
* Induction of mechanical brain injury as an animal model of [[post-traumatic epilepsy]]<ref>{{cite book |doi=10.1007/978-1-4939-3816-2_27 |chapter=Animal Models of Posttraumatic Seizures and Epilepsy |title=Injury Models of the Central Nervous System |series=Methods in Molecular Biology |year=2016 |last1=Glushakov |first1=Alexander V. |last2=Glushakova |first2=Olena Y. |last3=Doré |first3=Sylvain |last4=Carney |first4=Paul R. |last5=Hayes |first5=Ronald L. |volume=1462 |pages=481–519 |pmid=27604735 |pmc=6036905 |isbn=978-1-4939-3814-8 }}</ref>
* Injection of the [[neurotoxin]] [[6-hydroxydopamine]] to dopaminergic parts of the basal ganglia as an animal model of [[Parkinson's disease]].<ref name="pmid23175810">{{cite journal | vauthors=Halje P, Tamtè M, Richter U, Mohammed M, Cenci MA, Petersson P | title=Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations. | journal=Journal of Neuroscience| volume=32 | issue=47 | pages=16541–51 | year=2012 | pmid=23175810| pmc=6621755 | doi=10.1523/JNEUROSCI.3047-12.2012}}</ref>
* [[Immunisation]] with an auto-[[antigen]] to induce an [[immune response]] to model [[autoimmune diseases]] such as [[Experimental autoimmune encephalomyelitis]]<ref name="pmid17943249">{{cite journal |last1=Bolton |first1=C. |title=The translation of drug efficacy from in vivo models to human disease with special reference to experimental autoimmune encephalomyelitis and multiple sclerosis |journal=Inflammopharmacology |date=October 2007 |volume=15 |issue=5 |pages=183–187 |doi=10.1007/s10787-007-1607-z |pmid=17943249 }}</ref>
* Occlusion of the [[middle cerebral artery]] as an [[animal models of ischemic stroke|animal model of ischemic stroke]]<ref name="pmid12442622">{{cite book |doi=10.1007/978-3-7091-6743-4_10 |chapter=Experimental Models in Focal Cerebral Ischemia: Are we there yet? |title=Research and Publishing in Neurosurgery |year=2002 |last1=Leker |first1=R. R. |last2=Constantini |first2=S. |series=Acta Neurochirurgica. Supplement |volume=83 |pages=55–59 |pmid=12442622 |isbn=978-3-7091-7399-2 }}</ref>
* Injection of blood in the [[basal ganglia]] of [[mus musculus|mice]] as a model for [[hemorrhagic stroke]]<ref name="pmid18586227">{{cite journal |vauthors=Wang J, Fields J, Doré S | title=The development of an improved preclinical mouse model of intracerebral hemorrhage using double infusion of autologous whole blood | journal=Brain Res | volume=1222 | pages=214–21 | year=2008 | pmid=18586227 | doi=10.1016/j.brainres.2008.05.058| pmc=4725309 }}</ref><ref name="pmid18193028">{{cite journal |last1=Rynkowski |first1=Michal A |last2=Kim |first2=Grace H |last3=Komotar |first3=Ricardo J |last4=Otten |first4=Marc L |last5=Ducruet |first5=Andrew F |last6=Zacharia |first6=Brad E |last7=Kellner |first7=Christopher P |last8=Hahn |first8=David K |last9=Merkow |first9=Maxwell B |last10=Garrett |first10=Matthew C |last11=Starke |first11=Robert M |last12=Cho |first12=Byung-Moon |last13=Sosunov |first13=Sergei A |last14=Connolly |first14=E Sander |title=A mouse model of intracerebral hemorrhage using autologous blood infusion |journal=Nature Protocols |date=January 2008 |volume=3 |issue=1 |pages=122–128 |doi=10.1038/nprot.2007.513 |pmid=18193028 }}</ref>
* [[Sepsis]] and [[septic shock]] induction by impairing the integrity of barrier tissues, administering live [[pathogens]] or [[toxins]]<ref name="Mouse Models of Sepsis and Septic S">{{cite journal |last1=Korneev |first1=K. V. |title=Mouse Models of Sepsis and Septic Shock |journal=Molecular Biology |date=18 October 2019 |volume=53 |issue=5 |pages=704–717 |doi=10.1134/S0026893319050108 |pmid=31661479 |doi-access=free }}</ref>
* Infecting animals with [[pathogens]] to reproduce human [[infectious diseases]]
* Injecting animals with [[agonists]] or [[Receptor antagonist|antagonists]] of various [[neurotransmitter]]s to reproduce human [[mental disorder]]s
* Using [[ionizing radiation]] to cause [[tumors]]
* Using gene transfer to cause [[tumors]]<ref>{{cite journal |vauthors=Eibl RH, Kleihues P, Jat PS, Wiestler OD | title=A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen | journal=Am J Pathol | volume=144 | issue=3 | pages=556–564 | year=1994 | pmid=8129041 | pmc=1887088}}</ref><ref>{{cite journal |vauthors=Radner H, El-Shabrawi Y, Eibl RH, Brüstle O, Kenner L, Kleihues P, Wiestler OD | title=Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose
 | journal=Acta Neuropathologica | volume=86 | issue=5 | pages=456–465 | year=1993 | pmid=8310796 | doi= 10.1007/bf00228580
 }}</ref>
* Implanting animals with [[tumor]]s to test and develop treatments using [[ionizing radiation]]
* [[artificial selection|Genetically]] selected (such as in [[diabetes|diabetic]] [[mus musculus|mice]] also known as [[NOD mice]])<ref name="pmid15099561">{{cite journal |vauthors=Homo-Delarche F, Drexhage HA | title=Immune cells, pancreas development, regeneration and type 1 diabetes | journal=Trends Immunol. | volume=25 | issue=5 | pages=222–9 | year=2004 | pmid=15099561 | doi=10.1016/j.it.2004.02.012}}</ref>
* Various animal models for [[wikt:screening|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<ref name="pmid14702631">{{cite journal |last1=Hisaeda |first1=Hajime |last2=Maekawa |first2=Yoichi |last3=Iwakawa |first3=Daiji |last4=Okada |first4=Hiroko |last5=Himeno |first5=Kunisuke |last6=Kishihara |first6=Kenji |last7=Tsukumo |first7=Shin-ichi |last8=Yasutomo |first8=Koji |title=Escape of malaria parasites from host immunity requires CD4+CD25+ regulatory T cells |journal=Nature Medicine |date=January 2004 |volume=10 |issue=1 |pages=29–30 |doi=10.1038/nm975 |pmid=14702631 }}</ref><ref name="pmid16641443">{{cite journal |vauthors=Coppi A, Cabinian M, Mirelman D, Sinnis P | title=Antimalarial activity of allicin, a biologically active compound from garlic cloves | journal=Antimicrob. Agents Chemother. | volume=50 | issue=5 | pages=1731–7 | year=2006 | pmid=16641443 | doi=10.1128/AAC.50.5.1731-1737.2006 | pmc=1472199}}</ref><ref name="pmid16569221">{{cite journal |vauthors=Frischknecht F, Martin B, Thiery I, Bourgouin C, Menard R | title=Using green fluorescent malaria parasites to screen for permissive vector mosquitoes | journal=Malar. J. | volume=5 | issue= 1 | page=23 | year=2006 | pmid=16569221 | doi=10.1186/1475-2875-5-23 | pmc=1450296 | doi-access=free }}</ref>

Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied. These models are rare, but informative. Negative models essentially refer to control animals, which are useful for validating an experimental result. Orphan models refer to diseases for which there is no human analog and occur exclusively in the species studied.<ref name="pmid750165"/>

The increase in knowledge of the [[genome]]s of non-human [[primates]] and other [[mammals]] that are genetically close to humans is allowing the production of [[Genetic engineering|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.

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 [[symptom]]s of depression in patients. Depression, as other [[mental disorders]], consists of [[endophenotype]]s<ref name=endophenotype>{{cite journal | last1=Hasler | first1=G. | year=2004 | title=Discovering endophenotypes for major depression | journal=Neuropsychopharmacology | volume=29 | issue=10 | pages=1765–1781 | doi=10.1038/sj.npp.1300506| pmid=15213704 | doi-access=free }}</ref> that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand [[molecular]], [[genetics|genetic]] and [[epigenetic]] factors that may lead to depression. By using animal models, the underlying molecular alterations and the causal relationship between [[Heredity|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.<ref>{{cite book |doi=10.1007/7854_2010_108 |chapter=Animal Models of Depression: Molecular Perspectives |title=Molecular and Functional Models in Neuropsychiatry |series=Current Topics in Behavioral Neurosciences |year=2011 |last1=Krishnan |first1=Vaishnav |last2=Nestler |first2=Eric J. |volume=7 |pages=121–147 |pmid=21225412 |pmc=3270071 |isbn=978-3-642-19702-4 }}</ref><ref>{{cite journal |last1=Wang |first1=Qingzhong |last2=Timberlake |first2=Matthew A. |last3=Prall |first3=Kevin |last4=Dwivedi |first4=Yogesh |title=The recent progress in animal models of depression |journal=Progress in Neuro-Psychopharmacology and Biological Psychiatry |date=July 2017 |volume=77 |pages=99–109 |doi=10.1016/j.pnpbp.2017.04.008 |pmid=28396255 |pmc=5605906 }}</ref>