The SCID-ra mouse: rat T-cell differentiation in the severe combined immunodeficient mouse

The SCID-hu mouse model offers the possibility to study the human thymus in vivo in an isolated xenogeneic environment. Whilst studying the toxicology of the human thymus using the SCID-hu model, a "control" model to test for differences in toxicokinetics due to the different localization of the thymus is desirable when SCID-hu data have to be extrapolated to the normal human situation. For this reason, SCID-ra mice were constructed by implanting rat fetal or postnatal thymus and liver explants under the renal capsule of severe combined immunodeficient (SCID) mice. Implantation of rat fetal thymus in combination with fetal liver resulted in thymus grafts with a histological appearance that was virtually identical to that of normal age-matched rat thymus. T cells of rat origin were found in the circulating blood and lymphoid organs of the recipient mice. After implantation of postnatal thymus and liver, the thymus grafts showed a dysplastic morphology. These grafts were devoid of thymocytes and consisted mainly of thymic microenvironmental components and large numbers of thymic macrophages. Some SCID-ra mice showed signs of graft-versus-host (GVH) reactions in the skin. The incidence of GVH reactions was higher with increasing developmental stage of the donor material used for implantation.