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You are here Biopharmaceutical Glossary homepage/Search > Biology > Model & other organisms for biopharmaceutical research Model &
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Map amoeba: See Dictyostelium discoideum animal model: A laboratory animal useful for medical research because it has specific characteristics that resemble a human disease or disorder. Scientists can create animal models, usually laboratory mice, by transferring new genes into them. [NHGRI] Experts in the pharmaceutical industry, as well as some at the U.S. Food and Drug Administration (FDA), have identified inadequate animal models as being one of the major hurdles in drug discovery and development. Pharmaceutical companies have long used model organisms, both in preclinical studies as well as for toxicity testing. Now, beyond simply testing drugs in animals to ascertain their safety, researchers are increasingly seeking animal models not only of specific diseases, but also of the particular pathways being targeted. CHA Cambridge Healthtech Advisors, Model Animal Systems: Emerging Applications and Commercial Opportunities in Drug Discovery and Development, report 2004 Contrast with model organisms. Arabidopsis thaliana: The first plant genome to be completely sequenced. Not of agricultural significance, but a model system for plant development, genetics and physiology. [Nature 408 (6814): 816- 26, 14 Dec. 2000 Arabidopsis (brassica or mustard family) - The Arabidopsis Information Resource (TAIR) http://www.arabidopsis.org/ Caenorhabditis elegans (C.
elegans) :
Nematode worm, a model organism, the first multicellular
organism to have a completely sequenced genome (97 megabases of DNA with
19,099 predicted protein-coding genes) as of December 11 1998. [ C.
elegans Sequencing Consortium "Genome Sequence of the Nematode
C.
Elegans" Science 282:2012 Dec 11, 1998]
congenic mice: Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus. [MeSH, 1999] Dictyostelium discoideum (amoeba): Dictyostelium discoideum is a soil- living amoeba. The hereditary information is carried on six chromosomes with sizes ranging from 4 to 7 Mb resulting in a total of about 34 Mb of DNA, a multicopy 90 kb extrachromosomal element that harbors the rRNA genes, and the 55 kb mitochondrial genome. The estimated number of genes in the genome is 8,000 to 10,000 and many of the known genes show a high degree of sequence similarity to genes in vertebrate species. Trans- NIH Model Organisms Initiative Dictyostelium discoideum http://www.nih.gov/science/models/d_discoideum/ A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best- known species and is widely used in biomedical research. [MeSH, 1979] Dictybase, Northwestern Univ. US http://dictybase.org/ Part of the Virtual Library disease models: Genetically modified mice have proven effective in the identification of new gene function and of novel drug targets and appropriate disease models are powerful tools for validation of such targets while facilitating disease and patient stratification studies at the same time. There is an marked increase in the use of mouse and other models for translational research purposes and a drive toward expediting the in vivo evaluation of in vitro selected molecules by developing animal models more predictive of therapeutic efficacy. Drosophila: A genus of small, two- winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. [MeSH Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes. [MeSH, 1972] Despite the fact that Drosophila
is a much studied organism, Celera (working with BDGP Berkeley Drosophila
Genome Project annotators) identified thousands of new genes in
commercially important protein families such as kinases, ion channels,
secreted proteins, and G-protein coupled receptors during the sequencing
phase. Drosophila proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development. [MeSH, 2002] E. coli Escherichia coli: Common bacterium that has been studied intensively by geneticists because of its small genome size, normal lack of pathogenicity, and ease of growth in the laboratory. [DOE] The archetypal model organism...has revealed many fundamental principles of cell metabolism, macromolecular synthesis, and gene regulation. It is better characterized than any other cell. But there remains so much more to learn. [Kenneth Rudd 'New tools for an old workhorse" Nature Biotechnology 18: 1241-1242 Dec. 2000] A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM- NEGATIVE FACULTATIVELY ANEROBIC RODS) commonly found in the lower part of the intestine of warm- blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. MeSH The preeminent French scientist and 1965 Nobel laureate Jacques Monod famously remarked, "What's true for E. coli is true for an elephant."
http://www.amazon.com/Microcosm-coli-Science-Life/product-reviews/037542430X EUCOMM: European Commission consortium -- a €13M EU Framework Project is designed to help researchers understand the genetic make-up of complex diseases. A repository of mouse stem cells will be generated, each of which contains a mutation in one of the 20,000 or so genes in the mouse genome. The cells will be freely available to the entire scientific community. Wellcome Trust, Sanger Institute, UK press release, 2005 http://www.sanger.ac.uk/Info/Press/2005/051014-2.shtml See also Knockout Mouse Project KOMP, NorCOMM fly, fruit
fly: See Drosophila. GMO Genetically Modified Organism: Organisms whose GENOME has been changed by a GENETIC ENGINEERING technique. [MeSH, 2002] Often restricted to modification by biotechnology related techniques (though various forms of non- molecular agricultural and veterinary modifications have been practiced for centuries (plant hybridization, breeding of race horses, etc.). Related term transgenic Gene OntologyTM Consortium: Functional
genomics glossary knockout mice: Mice whose genome contains a gene whose function has been disrupted, or "knocked- out". A common method of producing disabled genes using recombinant DNA technology is by inserting an antibiotic resistance gene into the normal DNA sequence of a clone of the gene being studied. This disrupts the gene's action, thereby preventing it from making an active protein product. Cells in which this transfer is successful are then injected into mouse embryos, producing chimeric mice. These mice are bred to yield a strain in which all the cells contain the knocked- out gene. Knockout mice are used as animal models for various diseases, such as cystic fibrosis, and are helping to clarify the functions of the genes studied within the fields of immunology, cancer genetics, and developmental biology. Mesh, 1994 Knockout-mouse technology is considered an essential and standard technique in functional genomics and target validation. Knockout Mouse Project KOMP: A trans-NIH initiative that aims to generate a comprehensive and public resource comprised of mice containing a null mutation in every gene in the mouse genome. http://www.nih.gov/science/models/mouse/knockout/index.html Related terms: Functional genomics glossary See also EUCOMM, NorCOMMknockout rats: Nature, 19 May 2003 http://www.nature.com/news/2003/030512/full/030512-17.html knockout rats: Wikipedia http://en.wikipedia.org/wiki/Knockout_rat mice: See congenic mice, knockout mice, mouse model organisms: Organisms used as models for studying the biological processes underlying states of health and disease, as well as the effects of particular compounds. Among the model organisms most commonly studied are mice, yeast, worms, fruit flies, and zebrafish. Because they are amenable to linking genes with cellular and physiological responses, simple model organisms are expected to be highly useful in understanding evolution and development with a biomedical perspective. CHI report Toxicogenomics: The Promise of Safer, Smarter Drug Development, 2002 Model
organisms are of key importance in both creating databases of gene sequences for
homology searching, and as platforms for investigating the biology of
genes of interest. Over the last few years, the use - and sophistication - of
such models has increased substantially. Findings from the recent publications
by the Human Genome Project and Celera Genomics support that homology
between human and animal- model genes and proteins is significant, particularly
among vertebrate species. Still, the conservation of genes and genetic pathways
between humans and invertebrate organisms is great enough that some of these
organisms have become critical model systems. mouse
Mus musculus, mice: Having
long been used as a model for genetic studies, offers a highly characterized
genetic system with many established inbred strains available for study.
Within the best mapped homologous mouse and human regions, the presence
and location of specific genes and gene families can be predicted in one
species based on mapping results obtained in the other. [Human Genome News,
Oak Ridge National Lab "Leaping across genomes" April - June 1996] http://www.ornl.gov/hgmis/publicat/hgn/v7n6/08mice.html Muridae: A family of the order Rodentia containing 250 genera including the two genera Mus and Rattus, from which the laboratory inbred strains are developed. The fifteen subfamilies are HESPEROMYINAE (New World mice and rats), Cricetinae, Spalacinae, Myospalacinae, Lophiomyinae, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, MICROTINAE (Arvicolinae), GERBILLINAE, Dendromurinae, Cricetomyinae, Murinae (Old World mice and rats), and Hydromyinae. [MeSH, 1982] murine: Mouse or rat. Pichia: Yeast-like ascomycetous fungi of the family Saccharomycetaceae, order SACCHAROMYCETALES isolated from exuded tree sap. [MeSH, 1991] rat, Rattus Norvegicus: Used extensively as a model organism for studying normal and disease processes in the human, primarily because of an extensive body of knowledge of rat physiological mechanisms, a significant number of rat models that mimic human diseases, the ease of breeding the rat, and the ability to generate inbred congenic and consomic rat strains. Once genes are identified in rats, pathophysiological mechanisms can be elucidated lending clues to the identification of human genetic counter- parts. [Rat Genome Database Request For Applications, NIH April 1999] http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-99-013.html The common name for the species Rattus norvegicus. [MeSH] MeSH also has
a number of additional terms for inbred rats.
Saccharomyces cerevisae (S. cerevisae): A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. MeSH, 1973 Yeast, perhaps the best understood eukaryotic organism at the molecular and cellular levels. However [forward genetics] had, prior to the systematic sequencing of the yeast genome (completed in 1996) resulted in the discovery of less than half of yeast genes. Now the yeast genomics community has turned to a large- scale, high- throughput approach to determining gene function, largely based on reverse genetics. Since yeast is the first eukaryotic model organism whose genome has been completely sequenced, many of the issues currently being faced by the yeast genomics community will eventually be of concern to people working with other organisms, including humans. Yeast can in certain cases serve as a model of human
disease ... The general rationale for this strategy is that many core cellular
processes (as opposed to processes involved in differentiation and development,
integration of tissues and organ systems, and activities of specialized cells
and tissues) are conserved between yeast and mammals. In fact, many molecules
and pathways that are known to be involved in processes that go awry in cancer
(e.g., the cell cycle and its control, DNA repair, telomere maintenance)
were either first discovered by yeast researchers, or research in yeast made
major contributions to their understanding.
slime mold: See Dictyostelium discoideum transgenic: An experimentally produced organism in which DNA has been artificially introduced and incorporated into the organism’s germ line, usually by injecting the foreign DNA into the nucleus of a fertilized embryo. [NHGRI] Plants can be transgenic as well as animal, though the field is not as highly developed. Transgenics can be a means of production as well as a way of systematic experimenting with knockouts. Related terms: knockout mice; knockdown, knockin, knockout; Genetic manipulation & disruption Genomics glossary crop genomics transgenic mice: Laboratory mice that have been produced from a genetically manipulated egg or embryo. MeSH, 1988 virtual organism: Becoming a virtual organism to learn about genetics, Association for Computing Machinery http://www.acm.org/crossroads/xrds13-1/organism.html worm: See Caenorhabditis elegans (C. elegans) Xenopus frog: The Xenopus embryo has long served as a major model for the study of embryonic development because of its numerous advantages, including external development, large size, identifiable blastomeres, and its ability to withstand extensive surgical intervention and culture in vitro. These advantages enable extensive investigation of the earliest embryonic patterning events. [Xenopus Initiative, NIH "Advantages of xenopus research"] http://www.nih.gov/science/models/xenopus/advantages.html An aquatic genus of the family, Pipidae, occurring in Africa and
distinguished by having black horny claws on three inner hind toes. MeSH, 1972
yeast: Perhaps the best- studied eukaryotic organism. Its experimental tractability, combined with the remarkable conservation of gene function throughout evolution, makes yeast the ideal model genetic organism. Yeast is a non- pathogenic model of fungal pathogens used to identify antifungal targets suitable for drug development and to elucidate mechanisms of action of antifungal agents. As a model of fundamental cellular processes and metabolic pathways of the human, yeast has improved our understanding and facilitated the molecular analysis of many disease genes. The completion of the Saccharomyces genome sequence helped launch the post- genomic era, focusing on functional analyses of whole genomes. Yeast paved the way for the systematic analysis of large and complex genomes by serving as a test bed for novel experimental approaches and technologies, tools that are fast becoming the standard in drug discovery research. [D. Ma, Applications of yeast in drug discovery, Progress Drug Research 57: 117- 162, 2001] If not otherwise specified generally refers to Saccharomyces cerevisae. Other species of yeast, including Schizosaccharomyces pombe are also studied. Narrower terms: pichia, Saccharomyces cerevisae zebrafish Danio rerio: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. MeSH, 1991 The zebrafish is a powerful model system for the genetic analysis of vertebrate embryogenesis, organ development, and disease. Its unique power is its tractable, phenotype driven mutation screens and readily accessible transparent embryos. Because of its facile forward genetics, zebrafish accelerates gene discovery; because of its accessible embryos, it promotes deep understanding of gene function; because of its phylogenetic position, it informs mechanisms of genome conservation. [Zebrafish Breakout Group, Non- Mammalian Models Workshop, NIH Feb. 1999] http://www.nih.gov/science/models/nmm/appb4.html Zebrafish breed quickly and remain
transparent, both useful for insights into genetics.
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