Conditional ablation of dendritic cells in mice: comparison of two animal models.

Abstract

Dendritic cells (DC) knockout in mice should be a powerful mean to appreciate the role of these cells in physiological or pathological situations. In order to generate such an animal model, we used a stategy based on the DC-specific expression of a suicide gene in transgenic mice. We used the herpes simplex virus type 1-thymidine kinase (HSV1-TK) which allows conditional ablation of dividing HSV1-TK expressing cells by converting the non toxic ganciclovir (GCV) into a toxic metabolite1,2. DC expression of HSV1-TK in transgenic mice was attempted with the HIV-LTR promoter which had been previously shown to preferentially direct the expression of a CAT transgene in Langerhans cells3. We generated LTR-TK transgenic mice expressing the HSV1-TK gene under the control of the HIV-LTR promoter. We showed a low but preferential expression of the transgene in DC, leading to DC depletion in spleen and thymus following GCV administration4. This depletion was often associated with a thymic atrophy and a wasting syndrome. To rule out the possibility that a transgene expression leakiness in different tissues could be responsible for these pathological findings, we analysed the effects of GCV treatment in syngenic normal mice engrafted with transgenic bone marrow cells. In this situation, HSV1-TK expression is limited to hematopoietic cells.