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Developmental and tissue-specific expression of human CD4 in transgenic rabbits
B W Snyder1, J Vitale, P Milos
1Exemplar Corporation, Bay Colony Corporate Center, Waltham, Massachusetts, USA.
Molecular Reproduction and Development
|April 1, 1995
Summary
Researchers created transgenic rabbits expressing human CD4 (hCD4) to model AIDS. These rabbits showed increased susceptibility to HIV-1 infection, paving the way for new diagnostic and therapeutic research.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- Understanding Acquired Immunodeficiency Syndrome (AIDS) is hindered by the lack of suitable small animal models for studying Human Immunodeficiency Virus type 1 (HIV-1) infection.
- Existing models do not fully replicate HIV-1 pathogenesis or allow for comprehensive testing of interventions.
Purpose of the Study:
- To develop a rabbit model for studying AIDS by creating transgenic rabbits expressing the human CD4 (hCD4) gene.
- To assess the expression and function of the hCD4 transgene in rabbits and evaluate their susceptibility to HIV-1 infection.
Main Methods:
- Generation of transgenic rabbits via microinjection of a transgene containing the hCD4 coding region and upstream regulatory sequences into 271 rabbit embryos.
- Detection of hCD4 transgene, RNA, and protein in peripheral blood lymphocytes (PBLs) of founder rabbits and their offspring.
- T-cell subset analysis to determine the cell-specific expression of hCD4.
- In vitro HIV-1 infection of PBLs from transgenic and non-transgenic rabbits to measure viral replication.
Main Results:
- The hCD4 transgene was successfully integrated and detected in five male and two female founder rabbits.
- Both hCD4 RNA and protein were expressed in PBLs of all five male founders and their F1 offspring, but not in females.
- hCD4 expression was restricted to rabbit CD4-expressing lymphocytes.
- PBLs from hCD4 transgenic rabbits produced higher levels of HIV-1 p24 core protein upon in vitro infection compared to non-transgenic controls.
- Transgenic rabbits demonstrated enhanced susceptibility to HIV-1 infection in vitro.
Conclusions:
- Transgenic rabbits expressing hCD4 were successfully generated, demonstrating appropriate gene expression in T-cells.
- These hCD4 transgenic rabbits exhibit increased susceptibility to HIV-1 infection in vitro, suggesting their potential as a valuable model for AIDS research.
- Further in vivo studies are ongoing to validate the utility of this model for understanding HIV-1 pathogenesis and testing therapeutic strategies.
