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Transgenesis

January 13, 2007

Transgenesis is a technology used to introduce a gene of interest into an animal model for study. [This article will use the mouse as an example animal] Cloned genetic material called a construct is created, for insertion into the mouse embryo. Expression is restricted to a specific tissue by fusing the candidate gene to a cardiac-specific promoter in the transgenic construct. To produce a stable genetic modification, the construct is injected into the pronucleus of a one-cell embryo. The embryo is then implanted into a pseudopregnant female mouse. Mouse pups are genotyped and the transgenic mice, the founders, are mated to produce the stable line (6). Transgenesis is typically used to induce overexpression of transcriptional levels of the candidate gene. However, neither the copy number nor the point of insertion can be controlled, and both the transgene and the native gene are expressed. Consequently, it is necessary for the transgene expression to be dominant over its homologue in order to produce a phenotype. Furthermore, DNA insertion can result in mutagenic effects in the flanking DNA, complicating any resultant phenotype. Hence, several independent founders are generated to check the levels and sites of transgene expression and compare the phenotypes. Transgenesis is typically used to investigate endogenous protein function and signal transduction pathways.

If transgenesis sounds a lot like gene therapy – thats because it is. The process I described is very similar to what could one day be used for germline gene therapy. Because of the expertise gained from generating transgenic mice, germline gene therapy may be more easily achieved than somatic gene therapy. However, the technology is still very crude at this point, and needs to be refined before therapeutic use in humans is possible.

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