Abstract
Manipulation of the rodent genome by deliberately inserting (transgenic) or removing (knockout) a gene of interest or indeed by selectively breeding animals with a spontaneous or random mutation producing a trait of interest has been developed over several years. Mouse “fanciers” have been selectively breeding interesting mice since the turn of the last century to produce a plethora of different background strains of the common house mouse (Mus musculus). Rat (Rattus norvegicus) strain development has also proceeded with selective breeding, although the range of strains is more limited. The deliberate and targeted manipulation of the mouse genome has been with us for over two decades, with the rat genome a more recent addition, and yet this technology has been limited to a very narrow range of genes. With the complete mapping of the mouse genome (and the rat genome soon to follow), the powerful techniques of transgenic and knockout rodent production can be applied to the numerous genes whose expression is altered in existing stroke models.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gordon, J. W., Scangos, G. A., Plotkin, D. J., Barbosa, J. A., and Ruddle, F. H. (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc. Natl. Acad. Sci. USA 77, 7380–7384.
Gossler, A., Doetschman, T., Korn, R., Serfling, E., and Kemler, R. (1986) Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc. Natl. Acad. Sci. USA 83, 9065–9069.
Letts, V. A., Felix, R., Biddlecome, G. H., et al. (1998) The mouse stargazer gene encodes a neuronal ca2+-channel gamma subunit. Nat. Genet. 19, 340–347.
Noebels, J. L., Qiao, X., Bronson, R. T., Spencer, C, and Davisson, M. T. (1990) Stargazer: a new neurological mutant on chromosome 15 in the mouse with prolonged cortical seizures. [Erratum appears in Epilepsy Res. (1992) 11, 72]. Epilepsy Res. 7, 129–135.
Hough, T. A., Nolan, P. M., Tsipouri, V., et al. (2002) Novel phenotypes identified by plasma biochemical screening in the mouse. Mammal. Genome 13, 595–602.
Nolan, P. M., Peters, J., Strivens, M., et al. (2000) A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat. Genet. 25, 440–443.
Davis, M., Mendelow, A. D., Perry, R. H., Chambers, I. R., and James, O. F. (1995) Experimental stroke and neuroprotection in the aging rat brain. Stroke 26, 1072–1078.
Sutherland, G. R., Dix, G. A., and Auer, R. N. (1996) Effect of age in rodent models of focal and forebrain ischemia. Stroke 27, 1663–1667.
Hogan, B., Beddington, R., Costantini, F., and Lacey, E. (1994) Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Plain View, NY.
Vagner, S., Galy, B., and Pyronnet, S. (2001) Irresistible IRES’attracting the translation machinery to internal ribosome entry sites [Review]. EMBO Rep. 2, 893–898.
Burcin, M. M. (1998) A regulatory system for target gene expression. Front. Biosci. 3, C1–C7.
Nagy, A. (2000) Cre recombinase: the universal reagent for genome tailoring [Review]. Genesis 26, 99–109.
Howland, D. S., Liu, J., She, Y. J., et al. (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc. Natl. Acad. Sci. USA 99, 1604–1609.
Gurney, M. E., Pu, H. F., Chiu, A. Y., et al. (1994) Motor neuron degeneration in mice that express a human cu,zn superoxide dismutase mutation. Science 264, 1772–1775.
Wang, X., Barone, F. C, White, R. F., and Feuerstein, G. Z. (1998) Subtractive cloning identifies tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) increased gene expression following focal stroke. Stroke 29, 516–520.
Yokota, N., Uchijima, M., Nishizawa, S., Namba, H., and Koide, Y. (2001) Identification of differentially expressed genes in rat hippocampus after transient global cerebral ischemia using subtractive cDNA cloning based on polymerase chain reaction. Stroke 32, 168–174.
Roth, A., Gill, R., and Certa, U. (2003) Temporal and spatial gene expression patterns after experimental stroke in a rat model and characterization of PC4, a potential regulator of transcription. Mol. Cell. Neurosci. 22, 353–364.
Rosand, J. and Altshuler, D. (2003) Human genome sequence variation and the search for genes influencing stroke. Stroke 34, 2512–2516.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Harper, A.J. (2005). Production of Transgenic and Mutant Mouse Models. In: Read, S.J., Virley, D. (eds) Stroke Genomics. Methods in Molecular Medicine, vol 104. Humana Press. https://doi.org/10.1385/1-59259-836-6:185
Download citation
DOI: https://doi.org/10.1385/1-59259-836-6:185
Publisher Name: Humana Press
Print ISBN: 978-1-58829-333-6
Online ISBN: 978-1-59259-836-6
eBook Packages: Springer Protocols