This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stacey, A Articles by Melton, D W Search for Related Content PubMed PubMed Citation Articles by Stacey, A Articles by Melton, D W

Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice.

Pharmaceutical Proteins Ltd., Roslin, Midlothian, Scotland.

ABSTRACT

The mouse alpha-lactalbumin gene has been replaced with the human gene by two consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn replaced by human alpha-lactalbumin. The end result is a clean exchange of defined DNA fragments with no other DNA remaining at the target locus. Targeted ES cells at each stage remained capable of contributing efficiently to the germ line of chimeric animals. Double replacement using HPRT-deficient ES cells and the HPRT selection system is therefore a powerful and flexible method of targeting specific alterations to animal genes. A typical strategy for future use would be to generate a null mutation which could then be used to produce multiple second-step alterations at the same locus.

This article has been cited by other articles:

• Li, X., Zhang, J., Gao, H., Vieth, E., Bae, K.-H., Zhang, Y.-P., Lee, S.-J., Raikwar, S., Gardner, T. A., Hutchins, G. D., VanderPutten, D., Kao, C., Jeng, M.-H. (2005). Transcriptional targeting modalities in breast cancer gene therapy using adenovirus vectors controlled by {alpha}-lactalbumin promoter. Molecular Cancer Therapeutics 4: 1850-1859 [Abstract] [Full Text]  
• Maass, K., Ghanem, A., Kim, J.-S., Saathoff, M., Urschel, S., Kirfel, G., Grummer, R., Kretz, M., Lewalter, T., Tiemann, K., Winterhager, E., Herzog, V., Willecke, K. (2004). Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43. Mol. Biol. Cell 15: 4597-4608 [Abstract] [Full Text]  
• Cases, S., Zhou, P., Shillingford, J. M., Wiseman, B. S., Fish, J. D., Angle, C. S., Hennighausen, L., Werb, Z., Farese, R. V. Jr (2004). Development of the mammary gland requires DGAT1 expression in stromal and epithelial tissues. Development 131: 3047-3055 [Abstract] [Full Text]  
• Kato, G., Maeda, S. (2003). Production of Mouse ES Cells Homozygous for Cdk5-Phosphorylated Site Mutation in c-src Alleles. J Biochem 133: 563-569 [Abstract] [Full Text]  
• van der Weyden, L., Adams, D. J., Bradley, A. (2002). Tools for targeted manipulation of the mouse genome. Physiol. Genomics 11: 133-164 [Abstract] [Full Text]  
• Harrison, C., Ketchen, A.-M., Redhead, N. J., O'Sullivan, M. J., Melton, D. W. (2002). Replication Failure, Genome Instability, and Increased Cancer Susceptibility in Mice with a Point Mutation in the DNA Ligase I Gene. Cancer Res. 62: 4065-4074 [Abstract] [Full Text]  
• Divoky, V., Liu, Z., Ryan, T. M., Prchal, J. F., Townes, T. M., Prchal, J. T. (2001). Mouse model of congenital polycythemia: Homologous replacement of murine gene by mutant human erythropoietin receptor gene. Proc. Natl. Acad. Sci. USA 98: 986-991 [Abstract] [Full Text]  
• Lin, C.-H., Tallaksen-Greene, S., Chien, W.-M., Cearley, J. A., Jackson, W. S., Crouse, A. B., Ren, S., Li, X.-J., Albin, R. L., Detloff, P. J. (2001). Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum Mol Genet 10: 137-144 [Abstract] [Full Text]  
• Wallace, H., Ansell, R., Clark, J., McWhir, J. (2000). Pre-selection of integration sites imparts repeatable transgene expression. Nucleic Acids Res 28: 1455-1464 [Abstract] [Full Text]  
• Ng, P., Baker, M. D. (1999). The Molecular Basis of Multiple Vector Insertion by Gene Targeting in Mammalian Cells. Genetics 151: 1143-1155 [Abstract] [Full Text]  
• Gschwind, M., Huber, G. (1998). Introduction of Hereditary Disease-Associated Mutations into the beta -Amyloid Precursor Protein Gene of Mouse Embryonic Stem Cells: a Comparison of Homologous Recombination Methods. Mol. Cell. Biol. 18: 4651-4658 [Abstract] [Full Text]  
• Hormuzdi, S. G., Penttinen, R., Jaenisch, R., Bornstein, P. (1998). A Gene-Targeting Approach Identifies a Function for the First Intron in Expression of the alpha 1(I) Collagen Gene. Mol. Cell. Biol. 18: 3368-3375 [Abstract] [Full Text]  
• Magin, T. M., Schroder, R., Leitgeb, S., Wanninger, F., Zatloukal, K., Grund, C., Melton, D. W. (1998). Lessons from Keratin 18 Knockout Mice: Formation of Novel Keratin Filaments, Secondary Loss of Keratin 7 and Accumulation of Liver-specific Keratin 8-Positive Aggregates. J. Cell Biol. 140: 1441-1451 [Abstract] [Full Text]  
• Liu, Y., Suzuki, K., Reed, J. D., Grinberg, A., Westphal, H., Hoffmann, A., Doring, T., Sandhoff, K., Proia, R. L. (1998). Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP). Proc. Natl. Acad. Sci. USA 95: 2503-2508 [Abstract] [Full Text]  
• Cohen-Tannoudji, M., Robine, S., Choulika, A., Pinto, D., El Marjou, F., Babinet, C., Louvard, D., Jaisser, F. (1998). I-SceI-Induced Gene Replacement at a Natural Locus in Embryonic Stem Cells. Mol. Cell. Biol. 18: 1444-1448 [Abstract] [Full Text]  
• ROHRER, D. K., KOBILKA, B. K. (1998). G Protein-Coupled Receptors: Functional and Mechanistic Insights Through Altered Gene Expression. Physiol. Rev. 78: 35-52 [Abstract] [Full Text]