sign in sign up
<<
Home , Model organism

Model Organisms

How can we learn about by studying non-humans? Evolutionary conservation of DNA and structure and functions Examples: a. function in Model Organisms/ b. human genes found in other organisms Research c. developmental processes are very similar

For lots of information about model organisms, see: http://www.ceolas.org/VL/mo/

Escherichia coli (E. coli, bacteria, “bugs”) Model Organism Traits

1. small size (so you can grow lots of them in the lab) 2. short cycle (so you can study many generations) 3. be able to generate a clonal population of organisms 4. ability to make mutations 5. ability to identify the mutated genes (inserting foreign DNA) Basic characteristics: 6. start with an organism that’s not too complicated rod shaped (2µm X 1µm; ~500 times smaller than an animal cell 7. easy to watch development as it happens in the intestine of many 8. lots of others using that model also so tools are developed grows in the lab on defined medium at 37ºC 9. inexpensive to maintain divides every 20 minutes

Escherichia coli (E. coli, bacteria, “bugs”) Advantages of using this organism: Eukaryotic cell very inexpensive (Animal or ) easy to mutagenize and introduce foreign DNA * 10-100 µm in diameter * linear DNA in nucleus used extensively as a tool for manipulation of DNA from all organisms * has easily frozen to maintain stocks Disadvantages: much simpler than animal cells single celled, so does not go through development Significant Contributions to science: Prokaryotic cell metabolism, DNA replication, transcription, translation mechanisms very similar to (Bacteria) those in animals * 1 µm in length studies with bacteria proved that DNA is genetic material * circular DNA, no nucleus * no organelles ***nearly everyone uses E. coli: an essential tool for research Bacteria as a tool (yeast)

Basic characteristics: approximately 3µm in diameter same yeast as used in bread and beer Grow on a plate grows in lab in defined medium at 30°C divides every 90 minutes

Saccharomyces cerevisiae (yeast) elegans () Advantages of using this organism: easy to mutagenize and introduce foreign DNA can be induced to mate, so you can do entire sequence is known easily frozen to maintain stocks it is a Limitations: not multicellular Basic characteristics: small size limits cell biological analyses adult is about 1mm in length Significant contributions to science: control, regulation, DNA replication in the wild lives in the dirt functional studies of human genes can often be done in yeast in the lab is grown in petri dishes and fed E. coli at room temp. life cycle is 3 days 2 sexes: self-fertilizing hermaphrodite and male

Caenorhabditis elegans (worms) melanogaster () Advantages of using this organism: only 1000 cells, yet has skin, , muscle, intestine, and gonads embryos, larvae, and adults are clear, making studies of development straightforward genome sequence is complete (done at Washington University) easy to introduce foreign DNA and knock out genes can easily be frozen to maintatin mutant stocks Limitations: Basic characteristics: although multicellular, not a adult is about 3mm in length Significant contributions to science: studies of (how a cell “knows” what type of cell to become) in the wild is seen around rotting fruit nervous system development in the lab is fed on yeast at 25°C control of (2002 Nobel prize to Sulston, Brenner, and Horvitz) life cycle takes about 12-14 days (flies) thaliana (mustard weed, plant) Advantages of using this organism: complex multicellular structures make it good for studying development mutant flies often have defects that are very easy to see well-developed nervous system allows for studies of behavior and learning sequenced genome Limitations: not a vertebrate don’t freeze well Significant contributions to science: Basic characteristics identification of many genes that control development in flies and higher organisms adult plant is about 6-10 inches tall understanding of circadian rhythms life cycle is 4-6 weeks genes involved in learning grown in the lab in small pots in dirt or defined medium

Arabidopsis thaliana (mustard weed, plant) Laws Governing the Use of Animals in Research Advantages of using this organism: short generation time for a plant; small, sequenced genome 1. Act seeds of mutant stocks can be stored long-term first written in 1966, amended several times since then can introduce foreign DNA, easy to make mutants covers all warm-blooded animals except: horses not used for reseach; Limitations: animals raised for food; and mice, , and (2002 amendment) not an economically relevant crop regulates the proper treatment of these animals: food, housing, anesthesia use, enrichment, record keeping Significant contributions to science: first plant genome sequenced each institution must have an internal animal care and use committee analysis of plant specific relevant to crops regulated by the United States Department of Agriculture aid development of genetically modified crops http://www.nabr.org/AnimalLaw/AWA/TheAct.htm

Laws Governing the Use of Animals in Research Danio rerio (, ) 2. Health Research Extension Act of 1985, "Animals In Research” Covers research funded by the National Institutes of Health (NIH) Covers all Must consider whether the research is relevant to advancement of human and/or animal health, knowledge, and the good of society Must consider whether other non-animal approaches are possible Must use the most relevant animal lowest on the phylogenetic (ie Basic characteristics lease like humans) adults are about 4cm long Avoid and distress to animals, use anaesthesia; euthanize animals that are in pain originally isolated from rivers in India and Pakistan Investigators must be properly trained grows in the lab in aquariums at 28ºC http://grants2.nih.gov/grants/ol young fish in the lab eat aw/references/phspol.htm#Hea lth%20Research%20Extension adults eat brine shrimp (sea monkeys!) %20Act%20of%201985 Danio rerio (zebrafish, fish) Advantages of using this organism: laevis (African clawed ) easy to mutagenize for genetic screens embryos are clear, so developmental processes can easily be watched is a vertebrate small size and large brood size allows for extensive mutant analysis not possible in mice Limitations: relatively long generation time of 10-12 weeks not a Significant contributions to science: mutations identified affecting neuronal, muscular, cardiovascular, and bone development may prove to be the best genetic system for studying vertebrate development

Xenopus laevis () Mus musculus () Advantages of using this organism: females can be induced to lay hundreds of eggs embryos are very large, so easy to surgically manipulate is a vertebrate eggs are large, so great for doing Limitations: long generation time of 1-2 years; breeding mutants not really feasible not a mammal Basic characteristics Significant contributions to science: basic understanding of vertebrate embryo development adults are about 10cm long studies performed on egg extracts live in the lab in cages in special animal facilities generation time is about 6 months animals used in research are specifically bred for that purpose

http://www.xenbase.org/index.html

Mus musculus (mouse) Mus musculus (mouse)

Advantages of using this organism: Washington University Animal Studies Committee Requirements mammal, vertebrate, very close to humans evolutionarily food and water must be available constantly and changed twice a week fairly straightforward to “knock out” a gene of interest bedding and cages must be changed twice a week Limitations: must be on 12 hour light: 12 hour dark cycle long generation time and large space requirements make large scale genetic up to 5 mice per cage experiments unwieldy animals must be observed daily, including weekends and holidays quite expensive to maintain (mouse costs can be up to $2 per mouse per day) Significant contributions to science: cages can not be stacked used especially in studies of the immune system no other animal can be present when a mouse is euthanized good model for studies animals given tumors must be checked daily animals showing signs of duress must be euthanized must follow guidelines for surgeries must use approved euthanizing procedures (canis familiaris) Dogs (canis familiaris) Some important discoveries made using dogs: Washington University Animal Studies Committee Requirements 1888: for dogs must be provided with : 1923: discovered either be in a cage 2X the size required by Animal Welfare Act 1943: vitamin K discovered or get 30 minutes of exercise three times per week on alternating days 1956: open heart surgery and cardiac pacemakers developed dogs housed in isolation must get exercise and human interaction every day 1957: first successful human bone marrow transplant based on years of experiments in dogs group housed dogs must have at least a minimum amount of floor space determined by the size of the Current Research using dogs refining transplant technologies Dog size! !Floor Area (sq. ft.) < l5kg !8 blindness (many dog breeds are susceptible to eye disorders that very closely !15-30 kg !12.1 resemble human disorders !> 30 kg ! 2 x (body length from tip of nose to tail base + 6”) 2 /144 gene *dogs used for research are specifically bred for that purpose, usually beagles

Macaca mulatta (macaque, rhesus ) Macaca mulatta (macaque, rhesus monkey) Advantages of studying this organism: very closely related to man Limitations extremely long life cycle makes genetic experiments nearly impossible very expensive to maintain (at least $15 per day per animal) Significant contributions to science: these and a few other monkeys are the only animal models for studying HIV very good model for neurobiology Basic characteristics used for studies of such as for ebola and Originate from India Reach sexual maturity at 3-4 years Live on average 16 years The National Sanctuary for Retired Research Eat vegetation, , and small animals http://www.primatesanctuarynsrrp.org/

Non-human primates Washington University Animal Studies Committee Requirements *must provide enrichment: social grouping required for some for some, other enrichement can be provided if research requires isolation enrichment: cage complexities, toys (rotated every 2 weeks), varied food items, foraging opportunities (ie puzzle feeders), interaction with humans *can not be restrained unless directed by vet or in approved protocol *quarterly psychological well- being assessment *surgery guidelines must be followed *multiple surgeries can only be done with ASC approval