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Model Organisms. Model Organism. Important features of all model organisms Short lifespan Small, easy and inexpensive to maintain Produce large numbers of offspring Development external as well as internal Availability of mutants History/previous experiments and discoveries

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Model organism
Model Organism

  • Important features of all model organisms

    • Short lifespan

    • Small, easy and inexpensive to maintain

    • Produce large numbers of offspring

    • Development external as well as internal

    • Availability of mutants

    • History/previous experiments and discoveries

    • Genome is sequenced

    • Homologues for large % of human disease genes

    • Exhibit complex behaviors

    • Few ethical concerns


The choice of a model organism depends on what question is being asked
The choice of a model organism depends on what question is being asked.

  • Specific species

  • Uniform from research lab to research lab

  • Ability to apply new knowledge to other organisms

  • Advance our understanding of

    • Cellular function

    • Development

    • Disease


  • Model organisms1
    Model Organisms being asked.

    • E. coli

    • Drosophila

    • Xenopus

    • Zebrafish

    • Mouse

    • C. elegans

    • Yeast

    • Arabidopsis


    The nematode worm caenorhabditis elegans
    The Nematode Worm being asked.Caenorhabditis elegans

    • In 1965, Sydney Brenner settled on the small nematode worm Caenorhabditis elegans to study the important questions of development and the molecular basis of behavior, because of their suitable characteristics.

    • Due to its simplicity and experimental accessibility, it is now one of the most completely understood metazoans.

    • What is unique to this organism is that wild-type individuals contain a constant 959 cells. The position of cells is constant as is the cell number.

    • If the 6th chromosome pair is XX, then C. elegans will be a hermaphrodite. A XO combination in the 6th chromosome pair will produce a male. Hermaphrodites can self-fertilize or mate with males but cannot fertilize each other. In nature, hermaphrodites are the most common sex.


    C elegans has a very rapid life cycle
    C. elegans being asked.has a very rapid life cycle

    • C.elegans is transparent. It is easy to track cells and follow cell lineages.

    • The genome size of C. elegans is about a hundred million base pairs. This is approximately 20X bigger than that of E. coli and about 1/30 of that of human.

    • At 25℃, fertilized embryos of C. elegans complete development in 12 hours and hatch into free-living animals capable of complex behaviors.

    • The first stage juvenile(L1) passes through four juvenile stages(L1-L4) over the course of 40 hours to become a sexually mature adult.




    C elegans s cell lineages

    • C. alternative developmental stage in which it forms what is called a dauer.elegans has a simple body plan. Its cell lineages are relatively few and well studied.

    C. elegans’s cell lineages

    • C. elegans has a simple body plan. Its cell lineages are relatively few and well studied.



    The cell death pathway was discovered in c elegans
    The cell death pathway was discovered in receptor tyrosine kinase signaling pathways that control cell proliferation. C. elegans

    • The most notable achievement to date in C. elegans research has been the elucidation of the molecular pathway that regulates apoptosis or cell death.

    • Analysis of the ced mutants showed that, in all but one case, developmentally programmed cell death is cell autonomous, that is, the cell commits suicide.



    Rnai was discovered in c elegans
    RNAi was discovered in development and disease and is the focus of intense research to develop therapeutics for the control of cancer and neurodegenerative diseases.C. elegans

    • In 1998 a remarkable discovery was announced. The introduction of dsRNA into C. elegans silenced the gene homologous to the dsRNA. It is significant in two respects.


    One is that RNAi appears to be universal since introduction of dsRNA into nearly all animal, fungal, or plant cells leads to homology-directed mRNA degradation.

    The second was the rapidity with which experimental investigation of this mysterious process revealed the molecular mechanisms.


    Bacteria
    Bacteria of dsRNA into nearly all animal, fungal, or plant cells leads to homology-directed mRNA degradation.

    • The attraction of bacteria such as E. coli or B. subtilis as experimental systems is that they are relatively simple cells and can be grown and manipulated with comparative ease.

    • Molecular biology owes its origin to experiments with bacterial model systems.


    Assays of bacterial growth
    Assays of bacterial growth of dsRNA into nearly all animal, fungal, or plant cells leads to homology-directed mRNA degradation.

    • Bacterial cells are large enough, about 2µm, in lengthto scatter light, allowing the growth of a bacterial culture to be measured conveniently in liquid culture by the change in optical density.


    • The number of bacteria can be determined by diluting the culture and plating the cells on solid (agar) medium in a petri dish. Knowing how many colonies are on the plate and how much the culture was diluted makes it possible to calculate the concentration of cells in the original culture.



    Baker s yeast saccharomyces cerevisiae
    BAKER’S YEAST known as plasmids. Saccharomyces cerevisiae

    • Unicellular eukaryotes offer many advantages as experimental model systems. The best studied unicellular eukaryote is the budding yeast S. cerevisiae.




    • The ability to make such precise changes in the genome allows very detailed questions concerning the function of particular genes or their regulatory sequences to be pursued with relative ease.

    • Because of its rich history of genetic studies and its relatively small genome, S. cerevisiae was chosen as the first eukaryotic organism to have its genome entirely sequenced. This landmark was accomplished in 1996.


    S cerevisiae cells change shape as they grow
    S. cerevisiae allows very detailed questions concerning the function of particular genes or their regulatory sequences to be pursued with relative ease.cells change shape as they grow


    • Simple microscopic observation of allows very detailed questions concerning the function of particular genes or their regulatory sequences to be pursued with relative ease.S. cerevisiae cell shape can provide information about the events occurring inside the cell.

    • A cell that lacks a bud has yet to start replicating its genome. A cell with a very large bud is almost always in the process of executing chromosome segregation.


    The fruit fly drosophila melanogaster drosophila has a rapid life cycle
    The Fruit Fly allows very detailed questions concerning the function of particular genes or their regulatory sequences to be pursued with relative ease.Drosophila melanogasterDrosophila has a rapid life cycle

    • The salient features of the Drosophila life cycle are a very rapid period of embryogenesis, followed by periods of larval growth prior to metamorphosis.


    • The allows very detailed questions concerning the function of particular genes or their regulatory sequences to be pursued with relative ease.Drosophila life cycle


    • One of the key processes that occurs during larval development is the growth of the imaginal disks, which arise from invaginations of the epidermis in mid-stage embryos.

    • Imaginal disks differentiate into their appropriate adult structures during metamorphosis (or putation).


    • Figure 21-16 Imaginal disks in development is the growth of the imaginal disks, which arise from invaginations of the epidermis in mid-stage embryos.Drosophila


    The first genome maps were produced for drosophila
    The first genome maps were produced for development is the growth of the imaginal disks, which arise from invaginations of the epidermis in mid-stage embryos.Drosophila

    • Morgan’s lab studies on Drosophila (1910) led to two major discoveries:

      • genes are located on chromosomes, and each gene is composed of two alleles that assort independently during meiosis;

      • genes located on separate chromosomes segregate independently, whereas those linked on the same chromosome do not.


    • Hermann J. Muller provided the first evidence that environmental factors can cause chromosome rearrangements and genetic mutations.

    • Bridges used the polytene chromosomes to determine a physical map of the Drosophila genome (the first produced for any organism).



    • A variety of additional genetic methods were create to establish the fruit fly as the premiere model organism for studies in animal inheritance.

    • For example, balancer chromosomes were created that contain a series of inversions relative to the organization of the native chromosome.




    Genetic mosaics permit the analysis of lethal genes in adult flies
    Genetic mosaics permit the analysis of lethal genes in adult flies

    • Mosaics are animals that contain small patches of mutant tissue in a generally “normal” genetic background.

    • The analysis of genetic mosaics provided the first evidence that Engrailed is required for subdividing the appendages and segments of flies into anterior and posterior compartments.

    • The most spectacular genetic mosaics are gynandromorphs.




    The yeast flp recombinase permits the efficient production of genetic mosaics
    The yeast FLP recombinase permits the efficient production of genetic mosaics

    • Drosophila possesses several favorable attributes for molecular studies and whole-genome analysis. Most notably, the genome is relatively small.

    • The frequency of mitotic recombination was greatly enhanced by the use of the FLP recombinase from yeast.




    It is easy to create transgenic fruit flies that carry foreign dna
    It is easy to create transgenic fruit flies that carry foreign DNA

    • P-elements are transposable DNA segments that are the causal agent of a genetic phenomenon called hybrid dysgenesis.






    The house mouse mus musculus
    The House Mouse, identify regulatory sequences such as those governing Mus musculus

    • The mouse enjoys a special status due to its exalted position on the evolutionary tree: it is a mammal and, therefore, related to humans.

    • The mouse provides the link between the basic principles, discovered in simpler creatures like worms and flies, and human disease.


    Mouse embryonic development depends on stem cells
    Mouse Embryonic Development Depends on Stem Cells identify regulatory sequences such as those governing

    • Their small size prohibits grafting experiments of the sort done in zebrafish and frogs, but microinjection methods have been developed for introducing.

    • Figure 21-23 shows an overview of mouse embryogenesis.



    It is easy to introduce foreign dna into the mouse embryo
    It Is Easy to Introduce Foreign DNA into the Mouse Embryo identify regulatory sequences such as those governing

    • DNA is injected into the egg pronucleus, and the embryos are places into the oviduct of a female mouse and allowed to implant and develop.

    • The injected DNA integrates at random positions in the genome




    Homologous recombination permits the selective ablation of individual genes
    Homologous Recombination Permits the Selective Ablation of Individual Genes

    • The single most powerful method of mouse transgenesis is the ability to disrupt, or “knock out,” single genetic loci. This permits the creation of mouse models for human disease.

    • Gene disruption experiments are done with embryonic stem (ES) cells



    Mice exhibit epigenetic inheritance
    Mice Exhibit Epigenetic Inheritance Individual Genes

    • Studies on manipulated mouse embryos led to the discovery of a very peculiar mechanism of non-Mendelian, or epigenetic, inheritance.

    • This phenomenon is known as parental imprinting.




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