Almost all advancements in biotechnology have become possible only because of these multicellular organisms, which are also called model organisms or just ‘model.’ These are non-human species that are used to study various biological phenomena, especially to research various human diseases.
What are Model Organisms?
Model organisms are studied to understand various biological processes in humans. Due to ethical issues, humans cannot be used as model organisms. The common descent of all living beings made it possible to study metabolic and developmental pathways in humans.
Characteristics of Model Organisms
To serve as a research model, an organism must have the following characteristics:
- It should be small in size and easy to manage in laboratory conditions.
- A model organism should have the ability to breed in large numbers.
- The short generation time of model organisms helps the researchers study different generations at once. Generation time is the time period between the birth of an individual and the birth of its offspring; in other words, we can say that generation time is the time period between two consecutive generations.
- Similarities of some genes between model organisms and humans help in finding out the characteristics or diseases associated with that particular gene.
- Organisms with a short life span are preferred, and they should have minimal growth/nutritional requirements.
- A model organism must have its whole genome sequenced, and it should be harmless to humans.
Examples of some multi-cellular organisms, which are used as research models, are:
- Fruit fly (Drosophila melanogaster)
- Nematode worm (Caenorhabditis elegans)
- Western clawed frog (Xenopus tropicalis)
- Mouse (Mus musculus)
- Zebrafish (Danio rerio)
- Guinea pig (Cavia porcellus)
1. Drosophila melanogaster (fruit fly)
You must have seen tiny flies sitting over rotten fruits and vegetables; these flies are called Drosophila melanogaster (fruit flies). These flies have now become a popular invertebrate model to study genetics. Many studies on fruit flies have shown that genetic material is present in chromosomes.
Why D. Melanogaster has become the ideal model organism?
- It has a short life span and generation time of 12 days.
- Their tiny size and minimal growth requirement enable the scientist to culture them easily in small labs.
- Throughout its lifetime, female drosophila can lay up to 50 eggs per day.
- They have a minimum nutritional requirement of a diet containing carbohydrates and protein (yeast extract).
- Their entire genome has been sequenced, and they have only 4 pairs of chromosomes. Genes can be easily manipulated, which allows scientists to understand the role of a particular gene; this makes them the perfect model for studying genetics.
- There is approximately 60% of genes similarity between fruit flies and humans. Many of the common genes are associated with cancer and other genetic disorders.
2. Caenorhabditis elegans (nematode worm)
Caenorhabditis elegans is a nematode with a transparent body of about 1 mm in length. It has an unsegmented, cylindrical body with a false coloem (pseudocoloem), and it lacks respiratory and circulatory systems. C. elegans was the first multicellular organism to have its whole genome mapped by the end of 1980. C. elegans has two sexes: male (XO) and hermaphrodite females (XX). These hermaphrodite worms have both male and female sex organs (ovatestis). Fertilization takes place internally.
Why C. elegans is considered to be a good model organism?
- It has a transparent body, which allows researchers to closely monitor the changes that happen at different stages of development.
- C. elegans, just like humans, react to things they like and things they do not like. This makes it a perfect model for behavioral studies in humans.
- Short life cycle of 2-3 weeks helps in monitoring developmental stages in a short span of time.
- C. elegans has two sexes; XO male and XX female hermaphrodite. These hermaphrodite females are capable of self-fertilization and can produce hundreds of offspring. This ability to self-fertilize contributes to its use as a model organism because it can self-fertilize and produce large numbers of offspring and are not dependent on males for fertilization.
- C. elegans are very small in size and have minimum nutritional requirements. They feed on bacteria, thus they can be grown easily in laboratories by making them feed on bacteria like E. coli.
- C. elegans can be stored in a frozen state at 80°C and then defrosted when needed for further studies.
- They act as a potential model organism in research studies like neurological disorders and heart and kidney diseases.
- Under favorable conditions, they can produce over 1,000 eggs per day.
Examples of studies done using C. elegans as a model organism
- Age-related neurological disorders like Parkinson’s disease are caused by the loss of dopaminergic neurons due to accumulation of α -synuclein protein in the form of lewy bodies. α -synuclein is a neuronal protein that helps in neurotransmission and is found in the brain, muscles, and other tissues. In PD misfolding of alpha synuclein leads to the formation of clumps, eventually damaging the brain cells. Genome of C. elegans does not have orthologues for α-synuclein; therefore, elegans can be used as a model organism to study the effect of overexpression of α-synuclein variants in C. elegans. Initially, it was thought that the accumulation of α-synuclein in the form of lewy bodies leads to neuron damage. However, a study on C. elegans has shown that soluble oligomers induce neurotoxicity, not the insoluble aggregates of α-synuclein.
- Mitochondrion, also known as the powerhouse of the cell, produces energy in the form of ATP molecules. Dysfunction of mitochondria can cause many serious diseases like Leigh syndrome, metabolic disorders, and mitochondrial myopathy. Elegans have many orthologous genes responsible for mitochondrial diseases in humans. Researches have found that suppressing these genes in C. elegans can lead to many developmental defects.
- Infecting C. elegans with S. typhimurium has shown that p38MAPK signaling is involved in the innate immune response against the bacteria.
3. MOUSE (Mus musculus)
Mice used in labs for research purposes are called laboratory rats or lab rats. Lab rat is a hybrid of 3 subspecies of Mus musculus: Mus musculus domesticus, Mus musculus musculus, and Mus musculus casteaneous. These lab rats have white (albino mice) or black fur, whereas wild mice have brown fur. Lab rats are less aggressive and lighter than wild mice.
Advantages of using the mouse as a model organism
- Its whole genome has been sequenced and due to 85% similarity with the human genome, M. musculus (mouse) is often considered to be a perfect model organism.
- Many research studies have been done on mice like neurodegenerative disorders, cancer research, aging, etc.
- They have a short gestation period of around 3 weeks and can give birth to 3 to 10 offspring at once.
Genetically modified mice or transgenic mice
Researchers can mutate or alter some genes of mice at certain stages of the development process. This helps to draw a conclusion about the function of a particular gene; these mice are called genetically modified mice or transgenic mice.
What are nude mice?
A nude mouse is a transgenic or genetically modified strain without a thymus gland. We know that thymus is responsible for the production and maturation of T cells, an important part of cell-mediated immunity. This results in compromised immunity due to a lack of T cells. They are produced in labs by disruption of the FOXN1 gene. FOXN1 gene is responsible for the development of hair, nails, and immunity in humans. They are used in labs to gain insights into topics like immune response, cancer, and AIDS.
4. Zebrafish (Danio rerio)
Danio rerio (zebrafish) is a freshwater fish commonly found in South Asia and is widely used as a vertebrate model organism in research studies. It is about 2.5 cm to 4 cm long. Males are slender and thinner than females. They are commonly found in streams, canals, ponds, and rice paddy fields. They are omnivorous in nature and feed on insect larvae, phytoplankton, worms, etc.
Factors that make Zebrafish an important model for research studies are:
- Zebrafish (Danio rerio) have been used as a model organism since the 1960s. Their whole genome has been sequenced; this enables the researchers study the functions of certain genes by creating mutations in them.
- Zebrafish is small in size, which makes them easy to handle even in small labs with a low budget.
- They require less maintenance and can produce a huge number of offspring weekly, which makes them a valuable model for drug screening.
- A transparent zebrafish larva helps in studying the development of internal structures.
- In zebrafish, fertilization occurs outside the female’s body (external fertilization), this helps researchers study and monitor the early stages of development.
- Zebrafish have been used to study the biological process behind certain diseases like cancer, muscular dystrophy, etc.
- There is a 70% genes similarity between zebrafish and humans, making it a perfect model to study diseases in humans.
- Zebrafish can repair their damaged heart muscles within few weeks. Scientists are exploring this unique ability of zebrafish and are trying to find out specific factors responsible for this. This can be a great achievement if we can find ways to repair the human heart.
- Zebrafish have all the organs involved in the metabolic process, and thus, they can be used to study many metabolism-related disorders in humans. Studies on diseases like non-alcoholic fatty liver, hepatic diseases, and type II diabetes mellitus have been carried out with zebrafish as an animal model.
5. Arabidopsis thaliana (thale cress)
A. thaliana (thale cress) is a vascular plant with white flowers. It is considered to be a popular model organism in plants and agricultural science. It was the first plant to have its whole genome mapped, which makes it a popular model to understand molecular biology, flowering, and development in plants.
Advantages of using thale cress as a model organism
- The small genome size of Arabidopsis thaliana (~135Mb) allows easy genetic mapping and because of its small size, it is easy to cultivate in a small space, and it produces a large number of seeds.
- It has been used to understand the interaction between plants and their disease-causing pathogens.
- It has a short generation time and limited growth requirement. They are easy to look after.
- A. Thaliana can act as a transformation vector for Agrobactreium tumifaciens and thus can be used in plant genetics. It helps in producing pathogen-resistant crops.
- Development is quite fast and takes only 5-6 weeks.
- Mutations can be done easily by treating seeds with mutagenic chemicals or by keeping them under certain radiations.
6. Xenopus Tropicalis (western clawed frog)
Xenopus tropicalis, also known as a western clawed frog, is a species of frog. Its natural habitat includes rivers, swamps, freshwater lakes, subtropical or tropical moist forests, etc. X. tropicalis is about 5 cm in length, and females are 20% larger than males. Their eyes are located high on their head. It has fully wedded feet with claws. The dorsal surface is dark brown in color with small black gray spots. It feeds on earthworms and insect larvae, while its tadpole feeds on zooplanktons. X. tropicalis has been used as a model to study early development in vertebrates.
Benefits of using Xenopus Tropicalis as a model organism
- Its whole genome has been sequenced, which makes it a popular model organism to study genetics and developmental biology in vertebrates.
- X. tropicalis has a short generation time of less than 5 months.
- X. tropicalis is smaller in size, so they don’t take too much space and can produce a large number of eggs (up to 3000) per spawn.
- In laboratories, ovulation can be induced artificially by injecting them with hormones.
- Embryos develop externally, which helps in studying all the stages of development. Manipulations can be done on embryos by exposing them to specific chemicals.
- Within few days, eggs can develop into transparent tadpoles, which makes it easy to study different stages of embryonic development using a microscope.
- X. tropicalis is diploid just like humans, and therefore, it has been used for studying comparative genetics, embryonic development, and cell biology.
7. Guinea pigs (Cavia porcellus)
The guinea pig is a species of rodent. Since the 17th century, various researches have been carried out on guinea pigs. But now, they are replaced by mice and lab rats. Many research studies like tuberculosis and scurvy have been done using guinea pigs as research models.
Example of research studies using Guinea pig as a model organism
- Guinea pigs are biologically similar to humans, which makes them a perfect model organism in research studies like nutritional research, effects of antibiotics, development of vaccines for TB and diphtheria, and Vitamin C discovery was done by using guinea pig as an animal model.
- Guinea pigs models have been used to study the pathogenesis of tuberculosis. When guinea pigs are infected by M. Tuberculosis bacteria, they develop primary lesions just like humans.