Contiguous gene deletion of Ptprk and Themis causes T-helper immunodeficiency (thid) in the LEC rat

Abstract

The LEC rat has a spontaneous mutation of T-helper immunodeficiency (thid), which causes a marked defect in T cell maturation from double positive (DP) to CD4 single positive (SP) cells in the thymus. Previously, we identified the contiguous gene deletion of Ptprk and Themis genes in the thid locus that causes the simultaneous loss of expression of both genes, and the exogenous Ptprk expression partially rescued this phenotype. To determine whether the deletion of Themis influences thid phenotype, bone marrow (BM) cells were transduced with lentiviral vector expressing Themis gene, and were transplanted into X-ray-irradiated LEC rats. Interestingly, the exogenous Themis expression rescued the development of CD4 SP cells as well as Ptprk. The result suggests that the deficiency of both genes is responsible for the thid mutation, and that both genes are indispensable for the development of SP cells from DP cells in the thymus.