VAT will be added later in the checkout.Tax calculation will be finalised during checkout. Development (2004). PubMed Central A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. This service operates on a first-come, first-served basis. Inducible Gene Targeting in Mice Using the Cre/lox System Brian Sauer Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Building 10, Room 9N119, Bethesda, Maryland 20892-1800 E-mail: sauerb@helix.nih.gov genetically alter the mouse genome with nucleotide Article 36, 921–924 (2004). Keller, C., Hansen, M. S., Coffin, C. M. & Capecchi, M. R. Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Nature 309, 255–256 (1984). Luciw, P. A., Bishop, J. M., Varmus, H. E. & Capecchi, M. R. Location and function of retroviral and SV40 sequences that enhance biochemical transformation after microinjection of DNA. (2021), Nature Reviews Genetics Nature 336, 348–352 (1988). Gene targeting in mouse embryonic stem cells has become the 'gold standard' for determining gene function in mammals. In the meantime, to ensure continued support, we are displaying the site without styles Generation of mice with genome…, Figure 1B. The versatility of this approach depends on the availability of mouse … Google Scholar. Astrat-egy for conditional, cell type-specific gene targeting was recently developed (2) that Biol. Gene-trapped mouse embryonic stem cell lines are available from several sources. Bunting, M., Bernstein, K. E., Greer, J. M., Capecchi, M. R. & Thomas, K. R. Targeting genes for self-excision in the germline. Hinnen, A., Hicks, J. Authors Hicham Bouabe 1 , Klaus Okkenhaug. A simple search in PubMed using the key words “gene targeting” and “mice” returns close to 30,000 entries (Jan 2016). Folger, K. R., Thomas, K. R. & Capecchi, M. R. Nonreciprocal exchanges of information between DNA duplexes coinjected into mammalian cell nuclei. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Proc. The Knockout Mouse Project. Verification of CRISPR editing and finding transgenic inserts by Xdrop indirect sequence capture followed by short- and long-read sequencing, Cre-Controlled CRISPR mutagenesis provides fast and easy conditional gene inactivation in zebrafish, TALEN‐mediated generation of The ability to specifically modify DNA sequences in the genome of mice through gene targeting has made the mouse a powerful and indispensable experimental tool for advancing biological and medical knowledge. Search. Deletion was complete in liver and nearly complete in lymphocytes … Leader in CRISPR gene editing. The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Ivanova E, Corona C, Eleftheriou CG, Bianchimano P, Sagdullaev BT. Postnatally, Atg-1- animals show a modest delay in glomerular maturation. Sci. You are using a browser version with limited support for CSS. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century Mario R. Capecchi Abstract | Gene targeting in mouse embryonic stem cells has become the ‘gold standard’ for determining gene function in mammals. Targeting transgenes into the ROSA26 locus, Introduction of gene cassettes of interest into…, National Library of Medicine Science 246, 799–803 (1989). Conditional mutagenesis in mice has recently been made possible through the combination of gene targeting techniques and site-directed mutagenesis, using the bacteriophage P1-derived Cre/loxP recombination system. In healthy mice that mutation may have one effect on mouse health but a different effect may be observed in APPPS1 mice. Designing Gene Targeting Vectors [Excerpted and modified from LePage DF and Conlon RA (2006) Animal models for disease: knockout, knock-in, and conditional mutant mice.Methods Mol Med 129:41-67] . (2021), Laboratory Animals A protocol for construction of gene targeting vectors and generation of homologous recombinant embryonic stem cells. Proc. SA: splice acceptor. However, there are disadvantages to gene targeting. Gene targeting Transgenic mice Knockout mice Reporter mice ES cell lines Targeting vector Cre/loxP FRT/FLP MultiSite Gateway Cloning This is … Development 131, 299–309 (2004). A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. knockout rat model, History of genome editing: From meganucleases to CRISPR. Thomas, K. R. & Capecchi, M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Generation of mouse conditional knockout alleles in one step using the. USA 97, 13702–13707 (2000). Summarized most common steps for…, Figure 1A. Brinster, R. L. et al. A targeting vector is typically composed of three basic units: (i) a 5’ homology arm; (ii) a gene marker for positive selection (e.g. Would you like email updates of new search results? Keller, C. et al. Online ahead of print. 4A). DNA-elements are not drawn to scale. Gene targeting by homologous recombination in ES cells is a powerful routine in mouse developmental genetics. 2, 1372–1387 (1982). Quant. Marker), such as thymidine kinase, diphtheria toxin fragment A (DT-A), or, if the positive selection marker is flanked by loxP sites, Cre recombinase gene (Cre). Greer, J. M. & Capecchi, M. R. Hoxb8 is required for normal grooming behavior in the mouse. Transgenic and Knockout Core personnel can inject gene-trapped mouse embryonic stem cells into blastocysts, with the resulting chimeras then bred to germline transmission of the desired mutation. Nature 346, 847–850 (1990). 1). Mice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. Biol. Cell. Gunne S, Heinicke U, Parnham MJ, Laux V, Zacharowski K, von Knethen A. Biomolecules. Barrow, J. R. et al. Nature Reviews Genetics Proc. CONTACT US "A better model is within reach." Summarized most common steps for isolation of mouse embryonic stem (ES) cells and…, Figure 1B. Get time limited or full article access on ReadCube. Epub 2009 Mar 11. Cell Tissue Res. 13, 2134–2140 (1993). Science 301, 363–367 (2003). Moon, A. M., Boulet, A. M. & Capecchi, M. R. Normal limb development in conditional mutants of Fgf4. Internet Explorer). 2021 Apr 15;529(6):1121-1134. doi: 10.1002/cne.25011. Careers. The floxed (loxP sites flanked) positive selection marker gene can be removed by expressing Cre recombinase in the recombinant ESCs or by crossing the chimeric mice with Cre-expressing transgenic mice (see also Fig. Smithies, O., Gregg, R. G., Boggs, S. S., Koralewski, M. A. Science 248, 1227–1230 (1990). (2021), Nature Communications Gene targeting in mice involves several important steps: Engineering a gene targeting construct Nucleic Acids Res. Thank you for visiting nature.com. LoxP structure and Cre recombinase-mediated…, Figure 3. Unlike in knockout animal models, a knockin will use ES cells to infiltrate a genetic muta… 18, 2614–2626 (2004). Capecchi, M. R. Generating mice with targeted mutations. Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow. Google Scholar. Numbered (1–3) blue rectangles: exons of the Roas26 locus. doi: 10.1093/nar/gkp112. 2021 Mar 8. doi: 10.1007/s00018-021-03800-2. Capecchi, M. R. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Nature 317, 230–234 (1985). Nature 292, 154–156 (1981). 8600 Rockville Pike Mol. Overview of gene targeting by homologous recombination. USA 78, 6376–6380 (1981). 2015 Sep;8(9):1155-66. doi: 10.1242/dmm.021204. Accessibility Epub 2020 Sep 10. Austin et al. Cell. Davis, A. P., Witte, D. P., Hsieh-Li, H. M., Potter, S. S. & Capecchi, M. R. Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. See this image and copyright information in PMC. Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells. Neuron 33, 23–34 (2002). When referring to stem cells, having the capacity to contribute to the formation of all cell types, such as embryonic stem cells. Genes Dev. Department of Human Genetics, Howard Hughes Medical Institute, University of Utah School of Medicine, 15 North 2030 East, Room 5100, Salt Lake City, 84112-5331, Utah, USA, You can also search for this author in 2018 May 15;48(5):835-836. doi: 10.1016/j.immuni.2018.05.002. Introduction of gene cassettes of interest into Roas26 locus by homologous recombination in embryonic stem cells. 49, 123–138 (1984). In this review, we will give an updated summary of the gene targeting technology and discuss some important considerations in the design of gene-targeted mice. Conditional gene targeting using the…, Figure 4. 13, 1524–1528 (1999). Production of a mouse model by gene targeting takes more time than by transgenics. & Mintz, B. 12, 3365–3371 (1992). & Capecchi, M. R. Analysis of homologous recombination in cultured mammalian cells in transient expression and stable transformation assays. ISSN 1471-0064 (online). Goddard, J. M., Rossel, M., Manley, N. R. & Capecchi, M. R. Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Arenkiel, B. R., Tvrdik, P., Gaufo, G. O. Zijlstra, M., Li, E., Sajjadi, F., Subramani, S. & Jaenisch, R. Germ-line transmission of a disrupted β2-microglobulin gene produced by homologous recombination in embryonic stem cells. Gene targeting has great fidelity to the genetics of the disease since the endogenous gene is targeted. As in the first strategy, researchers can track the activity of the artificial reporter gene to figure out the existing gene's normal pattern of activity in mouse tissues. Nature 375, 791–795 (1995). Koller, B. H., Marrack, P., Kappler, J. W. & Smithies, O. Figure 1A. Cell 22, 479–488 (1980). Suchmice carry a predesigned mutation in their germ line and are devoid of a particular gene product throughout ontogeny (1). Genes Dev. Conditional and Inducible Gene Targeting Conventional gene targeting, in which gene function is ablated in all cells of the body, is estimated (T.D.) Dis Model Mech. Cell Mol Life Sci. Mol. Since its inception, this technology has revolutionized the study of … Development 122, 3217–3228 (1996). & Kucherlapati, R. S. Insertion of DNA sequences into the human chromosomal β-globin locus by homologous recombination. A series of alleles that can be present at the same locus, which produces graded phenotypes. 2021 Jan;383(1):395-407. doi: 10.1007/s00441-020-03331-5. A mutation of which the phenotypic effects are less severe relative to a null mutation in the same gene. Olfactory signaling via trace amine-associated receptors. Wagner, T. E. et al. Crossover points are depicted by “X”. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. COVID-19 is an emerging, rapidly evolving situation. Sci. Mol. https://doi.org/10.1038/nrg1619, Expert Opinion on Drug Discovery Endocrine. Conditional gene targeting using the Cre/loxP recombination system, Figure 5. Google Scholar. We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg-1-). neomycin resistance gene (neo)); (iii) a 3’ homology arm; and (iv) a negative selection marker (neg. Studies of gene function in mice often involve theanalysis ofembryonicstem(ES) cell-derived gene-targeted mice. Affiliation 1 Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK. Nat Rev Genet 6, 507–512 (2005). Schmidt, E. E., Taylor, D. S., Prigge, J. R., Barnett, S. & Capecchi, M. R. Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Since its inception, this technology has revolutionized the study of Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Transgenic mice play a huge role in the identification and research process of evaluating characteristics of various diseases. sel. The author declares no competing financial interests. Nkx3.1 Sci. Wigler, M. et al. Gene targeting (also, replacement strategy based on homologous recombination) is a genetic technique that uses homologous recombination to modify an endogenous gene.The method can be used to delete a gene, remove exons, add a gene and modify individual base pairs (introduce point mutations).Gene targeting can be permanent or conditional. ingenious targeting laboratory is open and fully operational to work on new and existing animal model projects. Cre expression mediates then the deletion of the floxed intervening sequence, resulting in the expression of the transgene and a reporter gene. 17, 394–409 (2003). Genes Dev. Prevention and treatment information (HHS). Investigator-screened targeted clones will be expanded by the core, sent for chromosome counts, and microinjected into blastocysts for chimera production. Epub 2015 Jul 16. Mol. Practical Guide to Gene Targeting and Creating a Knockout Mouse Overview of the Creation of a Conventional Knockout Mouse. 26, 455–459 (2000). Schwartzberg, P. L., Goff, S. P. & Robertson, E. J. Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. One of the first questions we have to ask is what is a knockin and why is it deemed so useful in the world of genetic research and engineering. Natl Acad. Cell. Nature Genet. A floxed intervening sequence, neomycin (Neo)-polyadenylation signal sequences (pA), prevents the transcription of the transgene. Gu, H., Marth, J. D., Orban, P. C., Mossmann, H. & Rajewsky, K. Deletion of a DNA polymerase β-gene segment in T cells using cell type-specific gene targeting. Please enable it to take advantage of the complete set of features! To obtain PubMed Google Scholar. Genet. Using these c… Here I provide a personal account of the work that led to the generation of gene targeting which now lies at the centre of functional genomic analysis. Here, Cre was used to delete a segment of the DNA polymerase beta gene flanked by IoxP recombinase … Genes Dev. Deng, C., Thomas, K. R. & Capecchi, M. R. Location of crossovers during gene targeting with insertion and replacement vectors. Production of a mutation in mouse En-2 gene by homologous recombination in embryonic stem cells. Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Humanized mouse models, KO mice, and transgenic mice. Gordon, J. W., Scangos, G. A., Plotkin, D. J., Barbosa, J. Nature 294, 92–94 (1981). to have produced most of the first 1000 gene KO mice, but it has limitations. Here, Cre was used to delete a segment of the DNA polymerase beta gene flanked by IoxP recombinase recognition sites. Science 265, 103–106 (1994). Biol. Article Thomas, K. R. & Capecchi, M. R. Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Microinjection of a rabbit β-globin gene in zygotes and its subsequent expression in adult mice and their offspring. CAS J Comp Neurol. Thomas, K. R., Deng, C. & Capecchi, M. R. High-fidelity gene targeting in embryonic stem cells by using sequence replacement vectors. Deng, C. & Capecchi, M. R. Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. Mouse, rat, & rabbit models customized to your research. FOIA Furthermore, the use of recombination systems, such as Cre/loxP or FRT/FLP, enables conditional induction or suppression of gene expression of interest in a restricted period of mouse's lifetime, in a particular cell type, or in a specific tissue. CAS Natl Acad. Cell 44, 419–428 (1986). How do we Genetically modify Curr Protoc Mol Biol. Capecchi, M. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. The reporter gene facilitates to track the expression of the transgene. Investigator submits a targeting strategy and demonstrates a proven screening protocol. Typical gene targeting strategy, A targeting vector is typically composed of three basic…, Figure 3. Epub 2020 Nov 25. USA 78, 5016–5020 (1981). Gene targeting in mice: a review Methods Mol Biol. Ectodermal Wnt3/βcatenin signalling is required for the establishment and the maintenance of the apical ectodermal ridge. Levinson, B., Khoury, G., VandeWoude, G. & Gruss, P. Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Conditional Gene-Targeting in Mice: Problems and Solutions. Cell 51, 503–512 (1987). USA 75, 1929–1933 (1978). Nyabi O, Naessens M, Haigh K, Gembarska A, Goossens S, Maetens M, De Clercq S, Drogat B, Haenebalcke L, Bartunkova S, De Vos I, De Craene B, Karimi M, Berx G, Nagy A, Hilson P, Marine JC, Haigh JJ. Conditional gene targeting using the Cre/loxP recombination system (A) Cre-mediated inactivation of a gene of interest. B. The method uses an interferon-responsive promoter to control the expression of Cre recombinase. The human β-globin gene and a functional thymidine kinase gene in developing mice. Boulet, A. M. & Capecchi, M. R. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Cell Mol. Thomas, K. R., Folger, K. R. & Capecchi, M. R. High frequency targeting of genes to specific sites in the mammalian genome. All prices are NET prices. Cell 11, 223–232 (1977). Natl Acad. The ability to introduce DNA sequences (e.g., genes) of interest into the germline genome has rendered the mouse a powerful and indispensable experimental model in fundamental and medical research. USA 77, 7380–7384 (1980). Folger, K., Thomas, K. & Capecchi, M. R. Analysis of homologous recombination in cultured mammalian cells. While knock-in mice are considered superior when it comes to their benefits and ability for accurate genetic targeting, transgenic mice can be equally valuable depending on the applications they are used for. Conditional Gene-Targeting in Mice: Problems and Solutions Immunity. Since its inception, this technology has revolutionized the study of mammalian biology and human medicine. Greer, J. M., Puetz, J., Thomas, K. R. & Capecchi, M. R. Maintenance of functional equivalence during paralogous Hox gene evolution. 2020 Dec 17;10(12):1688. doi: 10.3390/biom10121688. The client provides the Core with a linearized targeting vector that contains a null or mutated gene of interest. The Gene Targeting Service (GTS) creates genetically engineered (“knock-out”) mice via homologous recombination in embryonic stem (ES) cells. In recent studies, two different groups each generated Rhbdf1 homozygous mutant mice, and reported conflicting results regarding the phenotypes [1, 18]; Christova and colleagues, using the definitive-null strategy, generated an Rhbdf1 loss-of-function mutation in two different inbred mouse strains: C57BL/6J and 129S6. Genome Res. 2006 Nov;Chapter 23:Unit 23.1. doi: 10.1002/0471142727.mb2301s76. Gene trapping in mouse embryonic stem cells is a powerful, cost-effective approach for creating large numbers of insertional mutations in mice. Biol. CAS Methods Mol Biol. 1). Our services can be ordered together or individually depending on the investigator's needs. Importantly, success is less assured with gene targeting … Nrf2-A Molecular Target for Sepsis Patients in Critical Care. A knockin mouse (KI mouse) has an element inserted into a specific locus in the genome. Proc. Wagner, E. F., Stewart, T. A. Cold Spring Harbor Symp. A specialized construct of the neomycin resistance (neo r) gene was introduced into an exon of a cloned fragment of the Hprt gene and used to transfect ES cells.Among the G418 r colonies, 1 1000 were also resistant to the base analog 6 … We mutated, by gene targeting, the endogenous hypoxanthine phosphoribosyl transferase (HPRT) gene in mouse embryo-derived stem (ES) cells. Biotechnology and Biological Sciences Research Council/United Kingdom. & Robertson, E. J. Conditional gene targeting using the Cre/loxP recombination system (A) Cre-mediated inactivation of a gene of interest. A. Bethesda, MD 20894, Copyright Cell. Epub 2020 Dec 16. Moon, A. M. & Capecchi, M. R. Fgf8 is required for outgrowth and patterning of the limbs. Privacy, Help 2009 Apr;37(7):e55. This is a vast literature, a number that shows the popularity and the utility of this technology. Nature Med. I would like to thank all those who have worked in my laboratory. PubMed the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in The mouse has been a favourite animal for genetic studies for many decades and was an obvious choice for the first attempts to introduce new genes into the mammalian genome. Get the most important science stories of the day, free in your inbox. Clipboard, Search History, and several other advanced features are temporarily unavailable. Biol. Left mouse: introduction of loxP sites into a genomic locus of interest by homologous recombination using embryonic stem cells (see also Fig. One major limitation of genetic studies in NOD mice has been the lack of germline competent embryonic stem cells (ESCs) that allow efficient gene targeting. Targeting transgenes into the ROSA26…, Figure 5. PubMed Natl Acad. Nature 342, 435–438 (1989). Wong, E. A. Gene targeting in the mouse: advances in introduction of transgenes into the genome by homologous recombination. After approval of investigator’s approach the core will initiate electroporation in mouse ES cells. Joyner, A. L., Skarnes, W. C. & Rossant, J. volume 6, pages507–512(2005)Cite this article. This site needs JavaScript to work properly. For example, a loss-of-function mutation can be introduced in the mouse genome, targeting a particular gene of interest. 2021 Jan;31(1):121-130. doi: 10.1101/gr.265439.120. & Capecchi, M. R. Hoxb1 functions in both motoneurons and target tissues to establish and maintain proper neuronal circuitry. Mol. Biol. The circadian clock and metabolic homeostasis: entangled networks. Knockins are typically used in biology, genetic research and cloning to replace a DNA sequence at a specific locus within the genome, as opposed to the less accurate transgenic methods of replacement. Nature 345, 78–80 (1990). involves precisely targeting a specific gene in the mouse and introducing a know alteration of that gene, usually the deletion of the gene and the insertion of a marker gene in its place (a gene knock-out by targeted homologous recombination). Natl Acad. Cell. Development 127, 989–996 (2000). Normal development of mice deficient in β2M, MHC class I proteins, and CD8+ T cells. Left mouse: introduction of loxP sites into a genomic locus of interest by homologous recombination using embryonic stem cells (see also Fig. & Ruddle, F. H. Genetic transformation of mouse embryos by microinjection of purified DNA. Nature 403, 661–665 (2000). 2013;1064:315-36. doi: 10.1007/978-1-62703-601-6_23. The method uses an interferon-responsive promoter to control the expression of Cre recombinase. Work in several laboratories had defined conditions for manipulating fertilized mouse eggs and blastocysts in culture. Mansour, S. L., Thomas, K. R. & Capecchi, M. R. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Sci. Wellik, D. M. & Capecchi, M. R. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. and JavaScript. 2002 Dec;19(3):229-38. doi: 10.1385/ENDO:19:3:229. The DNA sequences can be integrated into the genome randomly or into a specific locus by homologous recombination, in order to: (1) delete or insert mutations into genes of interest to determine their function, (2) introduce human genes into the genome of mice to generate animal models enabling study of human-specific genes and diseases, e.g., mice susceptible to infections by human-specific pathogens of interest, (3) introduce individual genes or genomes of pathogens (such as viruses) in order to examine the contributions of such genes to the pathogenesis of the parent pathogens, (4) and last but not least introduce reporter genes that allow monitoring in vivo or ex vivo the expression of genes of interest. 2013;1064:337-54. doi: 10.1007/978-1-62703-601-6_24. Proc. Nature 295, 568–572 (1982). 18, 2608–2613 (2004). to have produced most of the first 1000 gene KO mice, but it has limitations.9 In about 30% of the cases, KO mice exhibit embryonic or … Google Scholar. Evans, M. J. Sci. Learn more about how to create a custom knockin mouse model. LoxP structure and Cre recombinase-mediated recombinations, Figure 4. & Fink, G. R. Transformation of yeast. Unable to load your collection due to an error, Unable to load your delegates due to an error. Cell 33, 705–716 (1983). Conventional gene targeting, in which gene function is ablated in all cells of the body, is estimated (T.D.) Furthermore, any desired DNA sequence of interest (here green box) can be inserted between the homology arms of the targeting vector, in order to introduce it into the target genome by homologous recombination. Gene targeting in mouse embryonic stem cells has become the 'gold standard' for determining gene function in mammals. Bradley, A., Evans, M., Kaufman, M. H. & Robertson, E. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. 12, 2919–2923 (1992). ingenious targeting laboratory is open and fully operational to work on new and existing animal model projects. Conditional Gene-Targeting in Mice: Problems and Solutions. Nature Genet. Generation of mice with genome modification of interest using homologous recombinant ESC clones, Figure 2. Cell 27, 223–231 (1981). Does the choice of gene-targeting strategy affect the phenotype? Costantini, F. & Lacy, E. Introduction of a rabbit β-globin gene into the mouse germ line. Nature 338, 153–156 (1989). Somat. 7, 1086–1090 (2001). 12, 63–72 (1986). DeChiara, T. M., Efstratiadis, A. Folger, K. R., Wong, E. A., Wahl, G. & Capecchi, M. R. Patterns of integration of DNA microinjected into cultured mammalian cells: evidence for homologous recombination between injected plasmid DNA molecules. Homologous recombination between the targeting vector and the target cognate chromosomal region results in the disruption of one genomic copy of the targeted genomic locus and loss of the vector’s negative selection marker gene.
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