Abstract
The human genome has been almost completely sequenced, and at least 30,000 genes have been found (1). Systematic studies of gene expression patterns by using cDNA microarrays have provided a powerful approach to molecular dissection of cells and tissues by comparing expression levels of tens of thousands of these genes at a time. Even insight into signaling pathways has been gained (2,3). However, information about the in vivo function of the various genes, especially disease genes, still requires the development of animal models carrying particular mutations. Several mouse mutagenesis projects (see Chapter 13) have been started during the last decade, and the number of mutant mice generated by targeted mutagenesis in mouse embryonic stem (ES) cells has increased exponentially (4–7).
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
Venter J. C., Adams M. D., Myers E. W., et al. (2001) The sequence of the human genome. Science 291, 1304–1351.
Duggan D. J., Bittner M., Chen Y., Meltzer P., and Trent J. M. (1999) Expression profiling using cDNA microarrays. Nat. Genet. 21, 10–14.
Ferea T. L. and Brown P. O. (1999) Observing the living genome. Curr. Opin. Genet. Dev. 9, 715–722.
Justice M. J., Zheng B., Woychik R. P., and Bradley A. (1997) Using targeted large deletions and highefficiency N-ethyl-N-nitrosourea mutagenesis for functional analyses of the mammalian genome. Methods 13, 423–436.
You Y., Browning V. L., and Schimenti J. C. (1997) Generation of radiationinduced deletion complexes in the mouse genome using embryonic stem cells. Methods 13, 409–421.
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.
Hrabe de Angelis M. H., Flaswinkel H., Fuchs H., et al. (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat. Genet. 25, 444–447.
Wood S. A., Allen N. D., Rossant J., Auerbach A., and Nagy A. (1993) Noninjection methods for the production of embryonic stem cell-embryo chimaeras. Nature 365, 87–89.
McLaren A. Mammalian Chimeras, book section. Cambridge University Press Cambridge, UK, 1976.
Tarkowski A. K. (1961) Nature 190, 857.
Moustafa L. A. and Brinster R. L. (1972) Induced chimaerism by transplanting embryonic cells into mouse blastocysts. J. Exp. Zool. 181, 193–201.
Evans M. J. and Kaufman M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154–156.
Martin G. R. (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.
Beddington R. S. and Robertson E. J. (1989) An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 105, 733–737.
Bradley A., Evans M., Kaufman M. H., and Robertson E. (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309, 255–256.
Tanaka S., Kunath T., Hadjantonakis A. K., Nagy A., and Rossant J. (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282, 2072–2075.
Kubiak J. Z. and Tarkowski A. K. (1985) Electrofusion of mouse blastomeres. Exp. Cell Res. 157, 561–566.
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, 8424–8428.
Nagy A. and Rossant J. (2001) Chimeras and mosaics for dissecting complex mutant phenotypes. Int. J. Dev. Biol. 45, 577–582.
Hooper M., Hardy K., Handyside A., Hunter S., and Monk M. (1987) HPRTdeficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326, 292–295.
Torres R. M. and Kühn R. (1997) Laboratory Protocols for Conditional Gene Targeting. Oxford University Press Oxford.
Lawitts J. A. and Biggers J. D. (1993) Culture of preimplantation embryos. Methods Enzymol. 225, 153–164.
Erbach G. T., Lawitts J. A., Papaioannou V. E., and Biggers J. D. (1994) Differential growth of the mouse preimplantation embryo in chemically defined media. Biol. Reprod. 50, 1027–1033.
Carmeliet P., Ferreira V., Breier G., et al. (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435–439.
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.
Shimada H., Kaname T., Suzuki M., et al. (1999) Comparison of ES cell fate in sandwiched aggregates and co-cultured aggregates during blastocyst formation by monitored GFP expression. Mol. Reprod. Dev. 52, 376–382.
DePrimo S. E., Stambrook P. J., and Stringer J. R. (1996) Human placental alkaline phosphatase as a histochemical marker of gene expression in transgenic mice. Transgenic Res. 5, 459–466.
Goring D. R., Rossant J., Clapoff S., Breitman M. L., and Tsui L. C., (1987) In situ detection of beta-galactosidase in lenses of transgenic mice with a gammacrystallin/ lacZ gene. Science 235, 456–458.
Le Mouellic H., Lallemand Y., and Brulet P. (1990) Targeted replacement of the homeobox gene Hox-3.1 by the Escherichia coli lacZ in mouse chimeric embryos. Proc. Natl. Acad. Sci. USA 87, 4712–4716.
Okabe M., Ikawa M., Kominami K., Nakanishi T., and Nishimune Y. (1997) ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett. 407, 313–319.
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.
Hadjantonakis A. K., Gertsenstein M., Ikawa M., Okabe M., and Nagy A. (1998) Generating green fluorescent mice by germline transmission of green fluorescent ES cells. Mech. Dev. 76, 79–90.
Hadjantonakis A. K., Gertsenstein M., Ikawa M., Okabe M., and Nagy A. (1998) Non-invasive sexing of preimplantation stage mammalian embryos. Nat. Genet. 19, 220–222.
Godwin A. R., Stadler H. S., Nakamura K., and Capecchi M. R. (1998) Detection of targeted GFP-Hox gene fusions during mouse embryogenesis. Proc. Natl. Acad. Sci. USA 95, 13042–13047.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Humana Press Inc.
About this protocol
Cite this protocol
Maatman, R., Gertsenstein, M., de Meijer, E., Nagy, A., Vintersten, K. (2003). Aggregation of Embryos and Embryonic Stem Cells. In: Hofker, M.H., van Deursen, J. (eds) Transgenic Mouse. Methods in Molecular Biology™, vol 209. Humana Press. https://doi.org/10.1385/1-59259-340-2:201
Download citation
DOI: https://doi.org/10.1385/1-59259-340-2:201
Publisher Name: Humana Press
Print ISBN: 978-0-89603-915-5
Online ISBN: 978-1-59259-340-8
eBook Packages: Springer Protocols