Evaluating birth frequencies and embryonic lethality in transgenesis following pronuclear injection of HIV DNA

The likelihood that expression of a foreign gene in a mammalian cell is deleterious to viability is confronted whenever novel transgenic animals are made. A pathological response to transgene expression is even desired in transgenic mouse models of human disease. The derivation of HIV-transgenic mice in our laboratory using multiple recombinant forms of an HIV provirus has resulted in mixed success best explained by the variable toxicity of the different transgenes. Employing a standardized approach to pronuclear injections, experimental variation amongst recombinant HIV transgenes was documented in terms of the percentage of pregnancies following embryo transfer into pseudopregnant mice and the percentage of transplanted embryos leading to term births in these pregnant females (giving rise to an index of birth success, SI). Results compiled over 5 years suggested that the SI reflected transgene toxicity, in this case of HIV gene products early in embryogenesis. These observations have guided the design of productive transgenes for mouse models of HIV-related diseases and may be generally applicable in transgenesis.