model organism

Animal Models in Animal Models in Human DiseasesHuman Diseases

Sumayya M SaliSumayya M Sali

M.Sc. M.Sc. BiotechnologyBiotechnology

Model organismModel organism

A A model organismmodel organism is a non-human species is a non-human species that is extensively studied to understand that is extensively studied to understand particular biological phenomenon, with the particular biological phenomenon, with the expectation that discoveries made in the expectation that discoveries made in the organism model will provide insight into the organism model will provide insight into the workings of other organismsworkings of other organisms

Selecting a model organismSelecting a model organism

Model organisms are chosen on the Model organisms are chosen on the basis that basis that

1.1. they are amenable to experimental they are amenable to experimental manipulationmanipulation

2.2. they look for several traitsthey look for several traits like like size, generation time, accessibility, size, generation time, accessibility, manipulation, genetics, manipulation, genetics, conservation of mechanisms, and conservation of mechanisms, and potential economic benefitpotential economic benefit

Important model organismsImportant model organisms VirusesViruses

Phage LambdaPhage Lambda Phi X 174Phi X 174 - its - its genomegenome was the first ever to was the first ever to

be sequenced. The genome is a circle of 11 be sequenced. The genome is a circle of 11 genesgenes, 5386 , 5386 base pairsbase pairs in length. in length.

Tobacco mosaic virusTobacco mosaic virus

Important model organismsImportant model organisms

» ProkaryotesProkaryotes Escherichia coliEscherichia coli ( (E. coliE. coli) - This common, ) - This common, Gram-negativeGram-negative

gut bacterium is the most widely-used organism in gut bacterium is the most widely-used organism in molecular geneticsmolecular genetics. .

Bacillus subtilisBacillus subtilis - an - an endosporeendospore forming forming Gram-positiveGram-positive bacterium bacterium

Caulobacter crescentusCaulobacter crescentus - a bacterium that divides into - a bacterium that divides into two distinct cells used to study two distinct cells used to study cellular differentiationcellular differentiation. .

Mycoplasma genitaliumMycoplasma genitalium - a minimal organism - a minimal organism Vibrio fischeriVibrio fischeri - - quorum sensingquorum sensing, , bioluminescencebioluminescence and and

animal-bacterial animal-bacterial symbiosissymbiosis with with Hawaiian Bobtail SquidHawaiian Bobtail Squid SynechocystisSynechocystis, a photosynthetic , a photosynthetic cyanobacteriumcyanobacterium widely widely

used in used in photosynthesisphotosynthesis research. research. Pseudomonas fluorescensPseudomonas fluorescens, a soil bacterium that readily , a soil bacterium that readily

diversifies into different strains in the lab. diversifies into different strains in the lab.

Important model organismsImportant model organisms EukaryotesEukaryotes

ProtistsProtists Chlamydomonas reinhardtiiChlamydomonas reinhardtii - a unicellular - a unicellular green algagreen alga used used

to study to study photosynthesisphotosynthesis, , flagellaflagella and and motilitymotility, regulation of , regulation of metabolismmetabolism, cell-cell recognition and , cell-cell recognition and adhesionadhesion, response to , response to nutrient deprivationnutrient deprivation and many other topics. and many other topics. Chlamydomonas reinhardtiiChlamydomonas reinhardtii has a well-studied genetics, has a well-studied genetics, with many known and mapped mutants and expressed with many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic sequence tags, and there are advanced methods for genetic transformation and selection of genes. transformation and selection of genes.

Dictyostelium discoideumDictyostelium discoideum is used in is used in molecular biologymolecular biology and and geneticsgenetics (its (its genomegenome has been sequenced), and is studied has been sequenced), and is studied as an example of as an example of cell communicationcell communication, , differentiationdifferentiation, and , and programmed cell deathprogrammed cell death. .

Tetrahymena thermophilaTetrahymena thermophila - a free living freshwater - a free living freshwater ciliateciliate protozoanprotozoan. .

Emiliania huxleyiEmiliania huxleyi - a unicellular marine - a unicellular marine coccolithophorecoccolithophore alga, extensively studied as a model alga, extensively studied as a model phytoplanktonphytoplankton species. species.

Important model organismsImportant model organisms FungiFungi

• Ashbya gossypiiAshbya gossypii, cotton pathogen, subject of genetics , cotton pathogen, subject of genetics studies (polarity, cell cycle) studies (polarity, cell cycle)

• Aspergillus nidulansAspergillus nidulans, , moldmold subject of genetics studies subject of genetics studies • Coprinus cinereusCoprinus cinereus, , mushroommushroom (genetic studies of (genetic studies of

mushroom development, genetic studies of mushroom development, genetic studies of meiosismeiosis) ) • Neurospora crassaNeurospora crassa - orange bread - orange bread moldmold (genetic studies (genetic studies

of of meiosismeiosis, metabolic regulation, and , metabolic regulation, and circadian rhythmcircadian rhythm))• Saccharomyces cerevisiaeSaccharomyces cerevisiae, baker's , baker's yeastyeast or budding or budding

yeast (used in brewing and baking) yeast (used in brewing and baking) • Schizophyllum communeSchizophyllum commune - model for - model for mushroommushroom

formation. formation. • Schizosaccharomyces pombeSchizosaccharomyces pombe, fission yeast, (cell cycle, , fission yeast, (cell cycle,

cell polarity, RNAi, centromere structure and function, cell polarity, RNAi, centromere structure and function, transcription) transcription)

• Ustilago maydisUstilago maydis, dimorphic yeast and plant pathogen of , dimorphic yeast and plant pathogen of maizemaize (dimorphism, plant pathogen, transcription) (dimorphism, plant pathogen, transcription)

Important model organismsImportant model organisms PlantsPlants

Arabidopsis thalianaArabidopsis thaliana, currently the most popular , currently the most popular model plant. This herbaceous model plant. This herbaceous dicotdicot is a is a crucifercrucifer, a , a member of the member of the mustardmustard family. Its small stature and family. Its small stature and short generation time facilitates genetic studies,short generation time facilitates genetic studies, and and many phenotypic and biochemical mutants have many phenotypic and biochemical mutants have been mapped. Arabidopsis was the first plant to been mapped. Arabidopsis was the first plant to have its have its genomegenome sequencedsequenced. Its genome sequence, . Its genome sequence, along with a wide range of information concerning along with a wide range of information concerning ArabidopsisArabidopsis, is maintained by the , is maintained by the TAIRTAIR database database

Selaginella moellendorffiiSelaginella moellendorffii is a remnant of an ancient is a remnant of an ancient lineage of vascular plants and key to understanding lineage of vascular plants and key to understanding the evolution of land plants. It has a small genome the evolution of land plants. It has a small genome size (~110Mb) and its sequence will be released by size (~110Mb) and its sequence will be released by the Joint Genome Institute in early 2008. the Joint Genome Institute in early 2008.

Important model organismsImportant model organisms Brachypodium distachyonBrachypodium distachyon is an emerging is an emerging

experimental model grass that has many attributes experimental model grass that has many attributes that make it an excellent model for temperate cereals. that make it an excellent model for temperate cereals.

Lotus japonicusLotus japonicus a model a model legumelegume used to study the used to study the symbiosis responsible for symbiosis responsible for nitrogen fixationnitrogen fixation. .

MaizeMaize ( (Zea maysZea mays L.) is a cereal grain. It is a diploid L.) is a cereal grain. It is a diploid monocot with 10 large chromosome pairs, easily monocot with 10 large chromosome pairs, easily studied with the microscope. Its genetic features, studied with the microscope. Its genetic features, including many known and mapped phenotypic including many known and mapped phenotypic mutants and a large number of progeny per cross mutants and a large number of progeny per cross (typically 100-200) facilitated the discovery of (typically 100-200) facilitated the discovery of transposonstransposons ("jumping genes"). Many DNA markers ("jumping genes"). Many DNA markers have been mapped and the genome has been have been mapped and the genome has been sequenced. sequenced. ((GeneticsGenetics, , Molecular biologyMolecular biology, , AgronomyAgronomy))

Important model organismsImportant model organisms

Arabidopsis thalianaZea mays

Lemna gibba

Animal modelAnimal model

An An animal modelanimal model is a living, non-human is a living, non-human animal used during the research and animal used during the research and investigation of human disease, for the investigation of human disease, for the purpose of better understanding the purpose of better understanding the disease without the added risk of causing disease without the added risk of causing harm to an actual human being during the harm to an actual human being during the processprocess

Advantages of Animal Advantages of Animal Models:Models:

1. Short life span - react faster. age faster. 1. Short life span - react faster. age faster.

2. Can be sacrificed - entire disease process 2. Can be sacrificed - entire disease process studied. studied.

3. Sufficient numbers available - statistics. 3. Sufficient numbers available - statistics.

4. Infectious agents used without moral 4. Infectious agents used without moral constraints. constraints.

5. Interactions of various factors studied - 5. Interactions of various factors studied - physiology, anatomy known physiology, anatomy known

Types of Models:Types of Models:

1.1. ExperimentalExperimental - This type is surgically - This type is surgically induced, should mimic the disease being induced, should mimic the disease being studied, and be easily manipulated and readily studied, and be easily manipulated and readily reproducible. reproducible.

2.2. NegativeNegative - This type of model does not - This type of model does not develop the disease and is usually avoided develop the disease and is usually avoided

3.3. OrphanOrphan - This type of model includes diseases - This type of model includes diseases of animals which do not have human of animals which do not have human counterparts or disease similar to those in man counterparts or disease similar to those in man with dissimilar etiologies or pathogenesis with dissimilar etiologies or pathogenesis

4.4. SpontaneousSpontaneous - These naturally occurring - These naturally occurring diseases of animals which mimic those diseases of animals which mimic those occurring in man. Over 890 types have been occurring in man. Over 890 types have been reported. reported.

Factors to be Considered Factors to be Considered When Selecting an Animal When Selecting an Animal

for Research: for Research: 1.1. Species Availability Species Availability 2.2. Pathogenesis Pathogenesis 3.3. Life Span of the Species and the Life Span of the Species and the

Segment Best Suited Segment Best Suited 4.4. Anatomic Characteristics Anatomic Characteristics 5.5. Nutritional Requirements and Nutritional Requirements and

Habits Habits 6.6. Genetics Genetics 7.7. Polymorphism Polymorphism

Factors to be Considered Factors to be Considered When Selecting an Animal When Selecting an Animal

for Research:for Research:8.8. Reproduction Reproduction 9.9. Indigenous Factors Peculiar to a Indigenous Factors Peculiar to a

Species; Strain or Supplier Species; Strain or Supplier 10.10. Type of Agent Type of Agent 11.11. Schedule of Administration Schedule of Administration 12.12. State of Health State of Health 13.13. Environmental Requirements Environmental Requirements 14.14. Past Experience of Investigator Past Experience of Investigator 15.15. Caging Caging


InvertebratesInvertebrates Caenorhabditis elegansCaenorhabditis elegans, a , a nematodenematode, usually , usually

called C. elegans - an excellent model for called C. elegans - an excellent model for understanding the genetic control of understanding the genetic control of development and physiology. C. elegans development and physiology. C. elegans was the first multicellular organism whose was the first multicellular organism whose genome was completely sequencedgenome was completely sequenced


InvertebratesInvertebrates DrosophilaDrosophila, usually the species , usually the species

Drosophila melanogasterDrosophila melanogaster - a kind of - a kind of fruit flyfruit fly, , famous as the subject of genetics famous as the subject of genetics experiments by experiments by Thomas Hunt MorganThomas Hunt Morgan and and others. Easily raised in lab, rapid others. Easily raised in lab, rapid generations, mutations easily induced, generations, mutations easily induced, many observable mutations. Recently, many observable mutations. Recently, Drosophila has been used for Drosophila has been used for neuropharmacological researchneuropharmacological research

Animal modelAnimal model Arbacia punctulataArbacia punctulata, the purple-spined , the purple-spined

sea urchinsea urchin, classical subject of , classical subject of embryological studies embryological studies

AplysiaAplysia, a sea slug, whose ink release , a sea slug, whose ink release response serves as a model in response serves as a model in neurobiologyneurobiology and whose and whose growth conesgrowth cones serve as a model serve as a model of of cytoskeletalcytoskeletal rearrangements. rearrangements.

Loligo pealeiLoligo pealei, a squid, subject of studies of , a squid, subject of studies of nerve function because of its giant nerve function because of its giant axonaxon (nearly 1 mm diameter, roughly a thousand (nearly 1 mm diameter, roughly a thousand times larger than typical mammalian axons) times larger than typical mammalian axons)


Macrostomum lignanoMacrostomum lignano, a free-living, , a free-living, marine flatworm, a model organism for marine flatworm, a model organism for the study of stem cells, regeneration, the study of stem cells, regeneration, ageing, gene function, and the evolution ageing, gene function, and the evolution of sex. Easily raised in the lab, short of sex. Easily raised in the lab, short generation time, indetermined growth, generation time, indetermined growth, complex behaviourcomplex behaviour

Schmidtea mediterraneaSchmidtea mediterranea a freshwater a freshwater planarian; a model for regeneration and planarian; a model for regeneration and development of tissues such as the brain development of tissues such as the brain and germlineand germline


VertebratesVertebrates Guinea pigGuinea pig ( (Cavia porcellusCavia porcellus) - used by ) - used by

Robert KochRobert Koch and other early bacteriologists and other early bacteriologists as a host for bacterial infections, hence a as a host for bacterial infections, hence a byword for "laboratory animal" even though byword for "laboratory animal" even though less commonly used todayless commonly used today

Characteristics of Guinea Characteristics of Guinea Pigs Which Enhance Their Pigs Which Enhance Their

Use in ResearchUse in Research 1. 1. Long Gestation Period With Mature Central Long Gestation Period With Mature Central

Nervous System at BirthNervous System at Birth - Important for - Important for toxicology and teratology studies. toxicology and teratology studies.

2. 2. Sensitivity of Respiratory SystemSensitivity of Respiratory System - Important for - Important for asthma and environmental pollution studies. asthma and environmental pollution studies.

3. 3. Quiet. Calm DispositionQuiet. Calm Disposition - Important for - Important for entomology studies. Can be used to test entomology studies. Can be used to test repellents and insecticides, and as feeding source for repellents and insecticides, and as feeding source for biting insects. biting insects.

4. 4. Anatomy of the Guinea Pig Ear and Associated Anatomy of the Guinea Pig Ear and Associated StructuresStructures Important for inner ear studies Important for inner ear studies because it is easily dissected and exposed. because it is easily dissected and exposed.

5. 5. Vitamin C RequirementVitamin C Requirement - Important for wound - Important for wound healing. bone, tooth and atherosclerosis studies. healing. bone, tooth and atherosclerosis studies.

Characteristics of Guinea Characteristics of Guinea Pigs Which Enhance Their Pigs Which Enhance Their

Use in ResearchUse in Research 6. 6. Guinea Pig serumGuinea Pig serum - Possesses hemolytic - Possesses hemolytic

complement with higher activity levels than other complement with higher activity levels than other lab animals. Widely used as a source of complement lab animals. Widely used as a source of complement for complement fixation test. for complement fixation test.

7. 7. Susceptibility to Infectious DiseasesSusceptibility to Infectious Diseases - Can be - Can be used as sentinel animals because of their acute used as sentinel animals because of their acute susceptibility to Coxiella burnetii. Mycobacterium susceptibility to Coxiella burnetii. Mycobacterium sp. Listeriosis. sp. Listeriosis.

8. 8. Similar lmmune System to ManSimilar lmmune System to Man - Guinea Pig - Guinea Pig immune system possesses a similar antigen-immune system possesses a similar antigen-macrophage interaction to man and delayed macrophage interaction to man and delayed cutaneous hypersensitivity reaction. cutaneous hypersensitivity reaction.

9. 9. High Dietary RequirementsHigh Dietary Requirements - For folic acid. - For folic acid. thiamine. arginine and potassium make guinea thiamine. arginine and potassium make guinea pigs useful in nutrition studies. pigs useful in nutrition studies.

10. 10. Precocious YoungPrecocious Young - Good for germ free raising. - Good for germ free raising.

Specific Techniques and Specific Techniques and Use of Guinea Pigs in Use of Guinea Pigs in

ResearchResearch1. 1. Schultz-Dale techniqueSchultz-Dale technique - Sensitized guinea Pig uterus - Sensitized guinea Pig uterus

exposed to foreign protein releases histamine and smooth exposed to foreign protein releases histamine and smooth muscle contraction is measured. muscle contraction is measured.

2. 2. Preyer reflexPreyer reflex - To check for deafness. observe a cocking of ear - To check for deafness. observe a cocking of ear pinnae in response to Galton Whistle. pinnae in response to Galton Whistle.

3. 3. AnaphylaxisAnaphylaxis - Sensitized guinea pig develops acute shock. - Sensitized guinea pig develops acute shock. respiratory collapse and death within 2-5 minutes upon later respiratory collapse and death within 2-5 minutes upon later re-exposure to the antigen. re-exposure to the antigen.

4. 4. Antihistamine effectsAntihistamine effects of drugs can be evaluated in guinea of drugs can be evaluated in guinea pigs because of their high susceptibility to histamineinduced pigs because of their high susceptibility to histamineinduced gastric ulcers and histamine-induced bronchospasm. gastric ulcers and histamine-induced bronchospasm.

5. 5. Evaluation of analgesicsEvaluation of analgesics can be done by the use of radiant can be done by the use of radiant heat to produce flinching of the skin in the guinea pig. The heat to produce flinching of the skin in the guinea pig. The threshold of pain is determined by the time of exposure and it threshold of pain is determined by the time of exposure and it is compared with the threshold in the presence of the is compared with the threshold in the presence of the analgesic in question. analgesic in question.

6. 6. Evaluation of antitussive agentsEvaluation of antitussive agents using guinea pigs involves using guinea pigs involves inhalation of coughing agents such as ammonia, sulfur inhalation of coughing agents such as ammonia, sulfur dioxide. and citric acid. dioxide. and citric acid.

Mouse as a Model Mouse as a Model OrganismOrganism

Down SyndromeDown Syndrome : : The Ts65Dn mouse, developed The Ts65Dn mouse, developed at The Jackson Laboratory, mimics trisomy 21 and at The Jackson Laboratory, mimics trisomy 21 and exhibits many of the behavioral, learning, and exhibits many of the behavioral, learning, and physiological defects associated with the syndrome in physiological defects associated with the syndrome in humans, including mental deficits, small size, obesity, humans, including mental deficits, small size, obesity, hydrocephalus and thymic defectshydrocephalus and thymic defects. .

Cystic Fibrosis (CF)Cystic Fibrosis (CF) - - The The CftrCftr knockout mouse knockout mouse has helped advance research into cystic fibrosishas helped advance research into cystic fibrosis

Cancer Cancer - - The p53 knockout mouse has a disabled The p53 knockout mouse has a disabled Trp53Trp53 tumor suppressor gene that makes it highly tumor suppressor gene that makes it highly susceptible to various cancerssusceptible to various cancers

GlaucomaGlaucoma - - The DBA/2J mouse exhibits many of The DBA/2J mouse exhibits many of the symptoms that are often associated with human the symptoms that are often associated with human glaucoma glaucoma

Mouse as a Model Mouse as a Model OrganismOrganism

Type 1 DiabetesType 1 Diabetes: : Non-obese Diabetic (NOD) Non-obese Diabetic (NOD) mice are enabling researchers to identify IDDM mice are enabling researchers to identify IDDM susceptibility genes and disease mechanisms.susceptibility genes and disease mechanisms.

Type 2 DiabetesType 2 Diabetes: : The leading mouse models The leading mouse models for NIDDM and obesity research were all for NIDDM and obesity research were all developed at The Jackson Laboratory: developed at The Jackson Laboratory: Cpefat,Cpefat, Lepob,Lepob, LeprdbLeprdb and and tub.tub.

EpilepsyEpilepsy - - The "slow-wave epilepsy," or The "slow-wave epilepsy," or swe,swe, mouse is the only model to exhibit both of the two mouse is the only model to exhibit both of the two major forms of epilepsy: petit mal (absence) and major forms of epilepsy: petit mal (absence) and grand mal grand mal

Heart DiseaseHeart Disease : : the the ApoeApoe knockout mouse and knockout mouse and C57BL/6J.C57BL/6J.

Animal modelAnimal model ChickenChicken ( (Gallus gallus domesticusGallus gallus domesticus) - used for ) - used for

developmental studies, as it is an developmental studies, as it is an amnioteamniote and and excellent for micromanipulation (e.g. tissue excellent for micromanipulation (e.g. tissue grafting) and over-expression of gene productsgrafting) and over-expression of gene products

CatCat ( (Felis cattusFelis cattus) - used in neurophysiological ) - used in neurophysiological research research

Dog (Dog (Canis lupus familiarisCanis lupus familiaris) - an important ) - an important respiratory and cardiovascular model, also respiratory and cardiovascular model, also contributed to the discovery of contributed to the discovery of classical conditioningclassical conditioning

HamsterHamster - first used to study kala-azar ( - first used to study kala-azar (leishmaniasisleishmaniasis))

Animal modelAnimal model LampreyLamprey - spinal cord research - spinal cord research Medaka (Medaka (Oryzias latipesOryzias latipes, the Japanese , the Japanese

ricefish) - an important model in ricefish) - an important model in developmental biology, and has the developmental biology, and has the advantage of being much sturdier than the advantage of being much sturdier than the traditional Zebrafishtraditional Zebrafish

Rat (Rat (Rattus norvegicusRattus norvegicus) - particularly useful ) - particularly useful as a toxicology model; also particularly useful as a toxicology model; also particularly useful as a neurological model and source of as a neurological model and source of primary cell cultures, owing to the larger size primary cell cultures, owing to the larger size of organs and suborganellar structures of organs and suborganellar structures relative to the mouserelative to the mouse

Animal modelAnimal model Rhesus macaqueRhesus macaque ( (Macaca mulattaMacaca mulatta) - used for ) - used for

studies on studies on infectious diseaseinfectious disease and cognition and cognition Cotton rat (Cotton rat (Sigmodon hispidusSigmodon hispidus) - formerly used in ) - formerly used in

polio research polio research Zebra finch (Zebra finch (Taeniopygia guttataTaeniopygia guttata) - used in the ) - used in the

study of the song system of songbirds and the study of the song system of songbirds and the study of non-mammalian auditory systems study of non-mammalian auditory systems

Takifugu (Takifugu (Takifugu rubripesTakifugu rubripes, a pufferfish) - has a , a pufferfish) - has a small genome with little junk DNA small genome with little junk DNA

The African clawed frog (The African clawed frog (Xenopus laevisXenopus laevis) - used ) - used in developmental biology because of its large in developmental biology because of its large embryos and high tolerance for physical and embryos and high tolerance for physical and pharmacological manipulation pharmacological manipulation

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