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FP7
HIVINNOV (Grant n°305137) is a collaborative research project supported by the European Union


The Human Immune System (HIS) mouse model

 

This model is used in the project by Pr. Ben Berkhout (Partner 5 : Academisch Medisch Centrum bij de Universiteit Amsterdam).

 

The in vivo testing of anti-HIV drugs and vaccines requires animal models systems. The macaque model is problematic for several reasons and regular mice cannot be infected with HIV-1. To solve this problem, humanized mouse models have been developed. These mice lack most of their own murine immune system and this is replaced by a human immune system. We use the NSG mice (scid IL-2R?c-/-) that lack B, T and NK cells, whilst their NOD genetic background creates a defect in macrophage activation and function.

 

NSG-HIS mice are constructed by engrafting hematopoietic progenitor cells (HPCs) derived from human fetal livers (see illustration). Newborn NSG pups (<5-day old) receive a sub-lethal total body irradiation one day before engraftment. The normal process of haematopoieses leads over 2 months to the generation of a relatively complete human immune system, including CD4+ T cells that are the major target cell for HIV-1 infection. HIV-1 can then be injected intraperitoneally and the impact of antiviral drugs can subsequently be tested by following the HIV viral load and human CD4+ T cell count in the blood.