HIV-1 expression during early mammalian development.
OBJECTIVE
Our long-term objective is to determine the consequences of HIV-1 expression in the mammalian fetus using the mouse as a model system. This study describes HIV gene expression in micro-injected and electroporated embryos during the pre-implantation period.


METHODS
Procedures were adopted to create a non-infectious HIV system to assay HIV long terminal repeat (LTR) activation in a non-human mammal.


METHODS
Two constructs (RSV promoter-HIV tat gene; HIV LTR-lac Z gene) were co-micro-injected (10 micrograms/ml each) into pronuclei of fertilized eggs or one nucleus of the two-cell stage and expression assessed after 2-5 days. The techniques of electroporation and micro-injection were compared for their ability to deliver the constructs expressed subsequently.


RESULTS
We found that HIV-1 expression, as monitored by beta-galactosidase production, can occur as early as the eight-cell to blastocyst stage. The intensity of HIV expression varied from high to low; the proportion of the embryo expressing HIV varied from half to only two cells. The material was too limited to allow a determination of integration.


CONCLUSIONS
The expression rate of the HIV-LTR was low, averaging slightly over 1%. The data demonstrate that the HIV-LTR can be activated in early mammalian development, even before implantation. This information is valuable to those studying HIV-transgenic mice, to those interested in factors governing HIV expression, and to those concerned about pathologies accompanying developmental expression of HIV.
Whitmer
K J
KJ
Department of Biology, California State University, San Francisco 94143.
Calarco
P G
PG
D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000382:microbiology*; D015696:Gene Products, tat / Q000096:biosynthesis; D015756:Genes, tat; D005822:Genetic Vectors; D015497:HIV-1 / Q000254:growth & development*; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008845:Microinjections; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D015053:Zygote / Q000382:microbiology; D001616:beta-Galactosidase / Q000096:biosynthesis; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D001616:beta-Galactosidase