Abstract
The ability to culture pluripotent cell lines, introduce into them targeted gene mutations, and then use these mutant cell lines to generate chimeric animals (1-4), has had a major impact on many fields; not least on ophthalmology and vision research (5-8). By generating animals lacking in the product of a single gene, we can examine the biochemical, physiological, and structural effects of its loss in vivo. Often this can yield insights, sometimes surprising, into human diseases caused by mutations in the same gene.
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References
Evans, M. J. and Kaufman, M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154ā156.
Doetschman, T., Gregg, R. G., Maeda, N., Hooper, M. L., Melton, D. W., Thompson, S., and Smithies, O. (1987) Targeted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330, 576ā578.
Bradley, A., Evans, M., Kaufman, M. H., and Robertson, E. J. (1984) Formation of germ-line chimeras from embryo-derived teratocarci-noma cell lines. Nature 309, 255, 256.
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W., and Roder, J. C. (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc. Natl. Acad. Sci. USA 90, 8424ā8428.
Humphries, M. M., Rancourt, D., Farrar, G. J., Kenna, P., Hazel, M., Bush, R. A., et al. (1997) Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nat. Genet. 15, 216ā219.
Brady, J. P., Garland, D., Duglas-Tabor, Y., Robison, W. G., Groome, A., and Wawrousek, E. F. (1997) Targeted disruption of the mouse aA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein Ī±B-crystallin. Proc. Natl. Acad. Sci. USA 94, 884ā889.
Redmond, T. M., Yu, S., Lee, E., Bok, D., Hamasaki, D., Chen, N., et al. (1998) Rpe65 is necessary for production of 11-cis-Vitamin A in the retinal visual cycle. Nat. Genet. 20, 344ā350.
Wang, T., Lawler, A. M., Steel, G., Sipila, I., Milam, A. H., and Valle, D. (1995) Mice lacking ornithine-delta-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration. Nat. Genet. 11, 185ā190.
Inana, G., Totsuka, S., Redmond, T. M., Dougherty, T., Nagle, J., Shiono, T., et al. (1986) Molecular cloning of human ornithine ami-notransferase mRNA. Proc. Natl. Acad. Sci. USA 83, 1203ā1207.
Deng, C. and Capecchi, M. R. (1992) Re-examination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. Mol. Cell. Biol. 12, 3365ā3371.
Thomas, K. R. and Capecchi, M. R. (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503ā512.
Mansour, S. L., Thomas, K. R., and Capecchi, M. R. (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336, 348ā352.
Tybulewicz, V. L., Crawford, C. E., Jackson, P. K., Bronson, R. T., and Mulligan, R. C. (1991) Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65, 1153ā1163.
Robertson, E. J. (ed.) (1987), Teratocarcinomas and Embryonic Stem Cells: A Practical Approach. IRL Press, Oxford, England.
Pease, S. and Williams, R. I. (1990) Formation of germ-line chimeras from embryonic stem cells maintained with recombinant leukemia inhibitory factor. Exp. Cell. Res. 190, 209ā211.
Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M., and Rogers, D. (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688ā690.
Laird, P. W., Zijderveld, A., Linders, K., Rudnicki, M. A., Jaenisch, R., and Berns, A. (1991) Simplified mammalian DNA isolation procedure. Nucleic Acid Res. 19, 4293.
Simpson, E. M., Linder, C. C., Sargent, E. E., Davisson, M. T., Mobraaten, L. E., and Sharp, J. J. (1997) Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat. Genet. 16, 19ā27.
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Redmond, T.M. (2001). Generation of Knockout Animal Models. In: Rakoczy, P.E. (eds) Vision Research Protocols. Methods in Molecular Medicineā¢, vol 47. Humana Press. https://doi.org/10.1385/1-59259-085-3:215
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DOI: https://doi.org/10.1385/1-59259-085-3:215
Publisher Name: Humana Press
Print ISBN: 978-0-89603-837-0
Online ISBN: 978-1-59259-085-8
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