SpringerProtocols: Abstract: Overview: Gene Knockouts

Overview: Gene Knockouts

By: Paul J. Hertzog³, Ismail Kola⁴

Abstract

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The ability to generate a mouse with a targeted mutation in a desired gene has been one of the most important advances in understanding the function of gene products. Not only can gene disruption demonstrate the function of genes, but by disrupting cell development or survival it can also demonstrate the function of specific cell types. Some knockout mice are murine models of human genetic diseases and have proven that a single gene defect is capable of causing disease. In addition, the crossing of mice that are heterozygous or homozygous for specific gene mutations provides important information on human diseases that are caused by multiple genetic defects. In genetic terms, targeted gene disruption is directly complementary to (and arguably more direct than) using mutant strains of mice with a known phenotype to map and identify the disease-causing genes.

Affiliation(s): (3) Centre for Functional Genomics and Human Disease, Monash University, Melbourne, Australia
(4) Centre for Functional Genomics and Human Disease, Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia

Book Title: Gene Knockout Protocols

Series: Methods in Molecular Biology | Volume: 158 | Pub. Date: Jan-15-2001 | Page Range: 1-10 | DOI: 10.1385/1-59259-220-1:1

Subject: Genetics/Genomics

References

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1.	Folger, K. R., Wong, E. A., Wahl, G., and Capecchi MR. (1982) Patterns of integration of DNA microinjected into cultured mammalian cells: evidence of homologous recombination between injected plasmid DNA molecules. Mol. Cell. Biol. 2, 1372–1387.

2.	Capecchi, M. R. (1989) The new mouse genetics: altering the genome by gene targeting. Trends Genet. 5, 70–76.

3.	Evans, M. J. and Kaufman, M. H. (1981) Establishment in culture of pluripotent cells from mouse embryos. Nature 292, 154–156.

4.	Martin, G. (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad Sci. USA 78, 7634–7638.

5.	Bradley, A., Evans, M., Kaufman, M. H., and Robertson, E. (1984) Formation of germ-line chimeras from embryo derived teratocarcinoma cell lines. Nature 309, 255–256.

6.	Robertson, E., Bradley, A., Kuehn, M., and Evans, M. (1986) Germline transmission of genes introduced into cultured pluripotial cells by retroviral vector. Nature 323, 445–447.

7.	Doetschman, T., Gregg, R. G., Maelda, N., et al. (1987) Targeted correction of mutant HPRT gene in mouse embryonic stem cells. Nature 330, 576–578.

8.	Thomas, K. R. and Capecchi, M. R. (1987) Site directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51, 503–512.

9.	Mak, T., (ed.) (1998) Gene Knockout Factsbook, Academic Press, San Diego, CA.

10.	Hasty, P., Ramirez-Solis, R., Krumlauf, R., and Bradley, A. (1991) Introduction of a subtle mutation into the HOX-2.6 locus in embryonic stem cells. Nature 350, 243–246.

11.	Wu, H., Liu, X., and Jaenisch, R. (1994) Double replacement: strategy for efficient introduction of subtle mutations into the murine Colla-1 gene by homologous recombination in embryonic stem cells. Proc. Natl. Acad. Sci. USA 91, 2819–2823.

12.	Ernst, M., Gearing, D. P., and Dunn, A. R. (1994) Functional and biochemical association of Hck with the LIF/IL-6 receptor signal transducing subunit gp130 in embryonic stem cells. EMBO J. 13, 1574–1584.

13.	Donehower, L. A., Harvey, M., Slagle, B. L., et al. (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356, 215–221.

14.	Lieschke, G. J., Grail, D., et al. (1994) Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 84, 1737–1746.

15.	Stanley, E., Lieschke, G. J., Grail, D., et al. (1994) Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of haematopoiesis but develop a characteristic pulmonary pathology. Proc. Natl. Acad. Sci. USA. 91, 5592–5596.

16.	Blendy, J. A., Kaestner, K. H., Schmid, W., Gass, P. and Schutz, G. (1996) Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J. 15, 1098–1106.

17.	Hwang, S. Y., Hertzog, P. J., Holland, K. A., et al. (1995) A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons a and b and alters macrophage responses. Proc. Natl. Acad. Sci. USA 92, 11,284–11,288.

18.	Muller, U., Steinhoff, U., Luiz, F. L., et al. (1994) Functional role of type I and type II interferons in antiviral defense. Science 264, 1918–1921.

19.	de Haan, J. B., Bladier, C., Griffiths, P., et al. (1998). Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J. Biol. Chem. 273, 22,528–22,536.

20.	Lee, E. Y.-H. P., Chang, C.-Y., Hu, N., et al. (1992) Mice deficient for Rb are non-viable and show defects in neurogenesis and haematopoiesis. Nature 359, 288–294.

21.	Bassuk, A. G. and Leiden, J. M. (1997) The role of Ets transcription factors in the development and Function of the Immune system. Adv. Immunol. 64, 65–104.

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