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World J Stem Cells. Dec 31, 2009; 1(1): 22-29
Published online Dec 31, 2009. doi: 10.4252/wjsc.v1.i1.22
Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background
Ana Claudia Carstea, Melinda K Pirity, Andras Dinnyes
Ana Claudia Carstea, Genetic Reprogramming Group, Agricultural Biotechnology Center, Szent Györgyi A u. 4, H-2100 Gödöllö, Hungary
Melinda K Pirity, Andras Dinnyes, Biotalentum Ltd, Aulich L. u 26, H-2100 Gödöllö, Hungary
Andras Dinnyes, Molecular Animal Biotechnology Laboratory, Szent Istvan University, Pater K u 1, H-2103, Gödöllö, Hungary
Author contributions: Carstea AC conceived the idea and prepared the original draft; all three authors participated equally in creating the final manuscript.
Supported by Grants from EU FP6 (“MEDRAT”-LSHG-CT-2005-518240; “Artemis”, LSHM-CT-2006-037862; “AGLAEA”, LSHM-CT-2006-037554, “CLONET”, MRTN-CT-2006-035468), EU FP7 (“PartnErS”, PIAP-GA-2008-218205; “InduHeart”, EU FP7-PEOPLE-IRG-2008-234390; “InduStem”, PIAP-GA-2008-230675; “Plurisys”, HEALTH-F4-2009-223485); NKFP_07_1-ES2HEART-HU, No. OM-00202-2007 and NKTH/ANR TET Franco-Hungarian Bilateral Scientific and Technological Collaborative Project “Plurabit”
Correspondence to: Andras Dinnyes, DSc, Professor, Molecular Animal Biotechnology Laboratory, Szent Istvan University, Pater K u 1, H-2103, Gödöllö, Hungary.
Telephone: +36-20-5109632 Fax: +36-28-526243
Received: December 1, 2009
Revised: December 14, 2009
Accepted: December 21, 2009
Published online: December 31, 2009

In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression (“knock-out”), or to introduce mutant or modified alleles at the locus of interest (“knock-in”). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.

Keywords: Chimeras, Transgenic, Embryonic stem cells, Epigenetic changes, Germline competence, Induced pluripotent stem cells