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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-07-2298.

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Submitted July 9, 2003
Accepted August 28, 2003

Highly efficient lentiviral-mediated human cytokine transgenesis on the NOD/scid background

Isabel Punzon, Luis M Criado, Alfredo Serrano, Fernando Serrano*, and Antonio Bernad

Department of Immunology and Oncology, Centro Nacional de Biotecnologia del CSIC, Madrid, Spain

* Corresponding author; email: fserrano{at}cnb.aum.es.

Human neo-organ formation from stem cells can only be assayed by in vivo xenotransplants. The HuNOD/scid CD34+ cell transplant is a model that allows examination of hematopoietic tissue formation, although human hematopoietic cell maturation is abortive. Conventional humanization of the cytokine microenvironment has depended on generation of human cytokine-transgenic mice in strains appropriate for conventional plasmid microinjection, followed by backcrossing, a costly and time-consuming approach. Lentiviral vector infection of single cell embryos was recently reported to produce transgenic animals. Using this approach, we have generated direct hGM-CSF transgenic mice from lentivirus-microinjected NOD/scid embryos, with 68% efficiency and 100% penetrance; this allowed us to obtain NOD/scid transgenic mice with considerable savings of resources. This powerful technique should assist in producing novel mouse models for the study of human blood cell lineage development and other human neo-organs from stem cell xenotransplants for which a similar humanization rationale may be required.


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[Abstract] [Full Text] [PDF]



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