Transgene expression of green fluorescent protein and germ line transmission in cloned pigs derived from in vitro transfected adult fibroblasts.

Authors:
Brunetti D1, Perota A, Lagutina I, Colleoni S, Duchi R, Calabrese F, Seveso M, Cozzi E, Lazzari G, Lucchini F, Galli C.
In:
Source: Stem Cells
Publication Date: (2008)
Issue: 10(4): 409(19)
Research Area:
Cancer Research/Cell Biology
Stem Cells
Gene Expression
Basic Research
Cells used in publication:
Fibroblast, pig
Species: porcine
Tissue Origin: dermal
Platform:
Nucleofector® I/II/2b
Experiment
On the day of transfection cells were tripsinized, counted, resuspended in 100 L of nucleofector solution (Basic Nucleofector Kit, Prim. Fibroblasts; Amaxa, Cologne, Germany), mixed with 3 g of the same vector pCAGGS–MAR GFP (Fig. 1A–C) with different selector cassettes (NeoR, HygroBR, and PuroR) for the single transfection or with 1.5 g plasmid DsRED  1.5 g GFP for the cotransfection, transferred into the nucleofection cuvettes, and transfected with V-24 program (Nucleofector Amaxa).
Abstract
The pig represents the xenogeneic donor of choice for future organ transplantation in humans for anatomical and physiological reasons. However, to bypass several immunological barriers, strong and stable human genes expression must occur in the pig's organs. In this study we created transgenic pigs using in vitro transfection of cultured cells combined with somatic cell nuclear transfer (SCNT) to evaluate the ubiquitous transgene expression driven by pCAGGS vector in presence of different selectors. pCAGGS confirmed to be a very effective vector for ubiquitous transgene expression, irrespective of the selector that was used. Green fluorescent protein (GFP) expression observed in transfected fibroblasts was also maintained after nuclear transfer, through pre- and postimplantation development, at birth and during adulthood. Germ line transmission without silencing of the transgene was demonstrated. The ubiquitous expression of GFP was clearly confirmed in several tissues including endothelial cells, thus making it a suitable vector for the expression of multiple genes relevant to xenotransplantation where tissue specificity is not required. Finally cotransfection of green and red fluorescence protein transgenes was performed in fibroblasts and after nuclear transfer blastocysts expressing both fluorescent proteins were obtained.