Transgenic mice ubiquitously expressing human Fas ligand develop a slight form of graft-versus-host-like disease

AIM: To construct transgenic mice bearing human Fas ligand (FasL/CD95L) cDN A, and further explore the physiological effects of ubiquitous expression o f Fast on such animals. METHODS: Transgenic mice were produced by pronuclei microinjection method. Integration and transmission of transgene were iden tified by nest-PCR and Southern-blot analysis. Level of Fast mRNA was evalu ated by semi-quantitative RT-PCR analysis. Fast protein was detected by imm unofluorescence analysis. Morphological alterations in tissues were analyze d by histological examination. The percentage of alpha betaT cells in the s pleen was determined by flow cytometry analysis. RESULTS: Two independent f ounder mice bearing human Fast cDNA under the control of CMV promoter were generated healthily. Human Fast was moderately expressed in the majority of tissues examined in F1 heterozygotic mice. Although developing normally, a dult transgenic mice exhibited a slight form of graft-versus-host (GVH)-lik e disease characterized by many morphological abnormalities occurring local ly in the spleen, testis, lung and liver. In addition, the percentage of al pha betaT cells in the spleen was respectively decreased approximately by 3 2 % and 24 % in two independent transgenic lines, relative to wild-type mic e. CONCLUSION: U-biquitous expression of Fas ligand can lead to slight GVH- like disease.