Abstract
The main advances in immunology have been forged or underpinned by animal experiments. However, animal research now focuses excessively on one laboratory species, and there is too much redundant repetition and too few transfers from basic discovery to successful clinical application. These features can be improved markedly by placing more emphasis on biological relevance when evaluating animal models and by taking greater advantage of the unique experimental opportunities that are offered by large animals.
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Acknowledgements
We thank A. Pernthaner, B. Buddle, H. Townsend, V. Gerdts and P. Atkinson for constructive comments and suggestions during the preparation of this manuscript.
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Glossary
- CLOSED ANALYSIS OF GENE EXPRESSION
-
An analysis in which the number and identity of genes that can be detected is predetermined by the probe set used for detection, such as microarray hybridization.
- CpG MOTIFS
-
Unmethylated CpG dinucleotides flanked by specific nucleotide sequences that can bind to TLR9 or other surface receptors and activate various immune cells (B cells, monocytes, macrophages and dendritic cells). The flanking nucleotide sequences that confer optimal immunostimulatory activity to CpG dinucleotides vary between species. These motifs are known also as CpG-oligodeoxynucleotides (CpG-ODNs).
- DIFFERENTIAL DISPLAY
-
A method that is used to identify genes that are expressed differentially by different sets of cells. Messenger RNA species are amplified by polymerase chain reaction using sets of degenerate primers, resolved by denaturing polyacrylamide gel electrophoresis and cloned as complementary DNA.
- EST DATABASE
-
An annotated collection of ESTs (expressed sequence tags). ESTs are pieces of RNA of varying length isolated from cells and cloned as cDNA. The template RNA might be transcribed from either the coding or non-coding parts of the genome, and the relative abundance of a particular EST is a measure of transcriptional activity.
- MICROARRAY HYBRIDIZATION
-
A procedure in which the messenger RNA isolated from cells is labelled and hybridized to a large number of nucleic-acid probes — complementary DNA or oligonucleotides — that are printed as arrays of small spots on a solid surface that is usually similar in size to a microscope slide.
- OPEN ANALYSIS OF GENE EXPRESSION
-
An analysis in which there is no constraint on the number or identity of genes that can be detected, such as differential display or subtracted cDNA libraries.
- SOMATIC CLONING
-
A procedure in which the nucleus from a differentiated cell is transferred to the cytoplasm of an oocyte from which the pronucleus has been removed. The genome of the transferred nucleus directs the future development of the cloned individual.
- SUBTRACTED cDNA LIBRARY
-
A collection of complementary DNA clones corresponding to the messenger RNA species that are present in one cell or tissue type and that are not present in another type.
- TOLL-LIKE RECEPTORS
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(TLRs). A diverse family of type 1 transmembrane proteins, the extracellular domains of which contain leucine-rich repeat motifs. The cytoplasmic domains of TLRs are structurally similar to the mammalian interleukin-1 receptor family. TLRs are important in innate immune recognition — their ligands include a range of molecules that are found only in prokaryotes.
- ZOONOTIC DISEASE
-
An infectious disease that is transferred from animals to humans.
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Hein, W., Griebel, P. A road less travelled: large animal models in immunological research. Nat Rev Immunol 3, 79–84 (2003). https://doi.org/10.1038/nri977
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DOI: https://doi.org/10.1038/nri977
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