Abstract
The gene-targeting technology allows complete and selective inactivation of a specific gene to study the consequence of total absence of the gene product. The availability of such null-mutant mice enables investigators to identify the biological function of the gene product in physiological or pathophysiological conditions. This technology, popularly known as “gene knockout,” can also induce more subtle mutations at the targeted site of the genome.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Niimura, F., Labosky, P. A., Kakuchi, J., Okubo, S., Yoshida, H., Oikawa, T., et al. (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J. Clin. Invest. 96, 2947–2954.
Okubo, S., Niimura, F., Nishimura, H., Takemoto, F., Fogo, A., Matsusaka, T., and Ichikawa, I. (1997) Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J. Clin. Invest. 99, 855–860.
Matsusaka, T., Nishimura, H., Utsunomiya, H., Kakuchi, J., Niimura, F., Inagami, T., et al. (1996) Chimeric mice carrying’ regional’ targeted deletion of the angiotensin type 1A receptor gene. J. Clin. Invest. 98, 1867–1877.
Tsuchida, S., Matsusaka, T., Chen, X., Okubo, S., Niimura, F., Nishimura, H., et al. (1998) Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensin nullizygotes. J. Clin. Invest. 101, 755–760.
Chen, X., Li, W., Yoshida, H., Tsuchida, S., Nishimura, H., Takemoto, F., et al. (1997) Targeting deletion of angiotensin type 1B receptor gene in the mouse. Am. J. Physiol. 272, F299–304.
Ichiki, T., Labosky, P. A., Shiota, C., Okuyama, S., Imagawa, Y., Fogo, A., et al. (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377, 748–750.
Esther, C. R.,Jr., Howard, T. E., Marino, E. M., Goddard, J. M., Capecchi, M. R., and Bernstein, K. E. (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab. Invest. 74, 953–965.
Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., and Rajewsky, K. (1994) Deletion of DNA polymerase p gene segment in T cells using cell type-specific gene targeting. Science 265, 103–106.
Rajewsky, K., Gu, H., Kühn, R., Betz, U. A. K., Müller, W., Roes, J., and Schwenk, F. (1996) Molecular medicine in genetically engineered animals. Conditional gene targeting. J. Clin. Invest. 98, 600–603.
Mortensen, R. M., Conner, D. A., Chao, S., Geisterfer, L. A., and Seidman, J. G. (1992) Production of homozygous mutant ES cells with a single targeting construct. Mol. Cell. Biol. 12, 2391–2395.
Mortensen, R. M. and Seidman, J. G. (1994) Inactivation of G-protein genes: double knockout in cell lines. Methods Enzymol. 237, 356–366.
Wood, S. A., Allen, N. D., Possant, J., Auerbach, A., and Nagy, A. (1993) Non-injection methods for the production of embryonic stem cell-embryo chimaeras. Nature 365, 87–89.
Wood, S. A., Pascoe, W. S., Schmidt, C., Kemler, R., Evans, M. J., and Allen, N. D. (1993) Simple and efficient production of embryonic stem cell-embryo chimeras by coculture. Proc. Natl. Acad. Sci. USA 90, 4582–4585.
Pirity, M., Hadjantonakis, A., and Nagy, A. (1998) Embryonic stem cells: creating transgenic animals. Methods Cell Biol. 57, 279–293.
Friedrich, G. and Soriano, P. (1991) Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5, 1513–1523.
Zambrowicz, B. P., Imamoto, A., Fiering, S., Herzenberg, L. A., Kerr, W. G., and Soriano, P. (1997) Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc. Natl. Acad. Sci. USA 94, 3789–3794.
Villarreal, F. J., Kim, N. N., Ungab, G. D., Printz, M. P., and Dillmann, W. H. (1993) Identification of functional angiotensin II receptors on rat cardiac fibloblasts. Circulation 88, 2849–2861.
Matsusaka, T., Katori, H., Inagami, T., Fogo, A., and Ichikawa, I. (1999) Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice. J. Clin. Invest. 103, 1451–1458.
Sawai, S., Shimono, A., Hanaoka, K., and Kondoh, H. (1991) Embryonic lethality resulting from disruption of both N-myc alleles in mouse zygotes. New Biol. 3, 861–869.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Humana Press Inc.
About this protocol
Cite this protocol
Takaya, J., Matsusaka, T., Ichikawa, I. (2001). Production and Use of Chimeric Mice. In: Wang, D.H. (eds) Angiotensin Protocols. Methods in Molecular Medicine™, vol 51. Humana Press. https://doi.org/10.1385/1-59259-087-X:41
Download citation
DOI: https://doi.org/10.1385/1-59259-087-X:41
Publisher Name: Humana Press
Print ISBN: 978-0-89603-763-2
Online ISBN: 978-1-59259-087-2
eBook Packages: Springer Protocols