ORP4L knockout prevents HTLV-1 oncogene Tax-induced T-cell leukemia in mice. (A) Western blot analysis of Tax and ORP4L expression in normal human T cells and T cells of patients with ATL. (B) Quantitative PCR (qPCR) analysis of ORP4L expression in normal human T cells (n = 5) and human ATL T cells (n = 37). (C) Western blot analysis of ORP4L expression in HTLV-1–infected human T cells (left) and human T cells infected with a lentivirus carrying Tax, HBZ, or both. T cells were infected with HTLV-1 or transduced with lentivirus and cultured in vitro for 16 weeks. (D) The targeting construction used to generate the T-cell–expressing Tax knockin mice. (E) Schematic representation of mouse line crossing strategy. (F) Western blot analysis of the expression of ORP4L in T-cells from 2-month-old WT, LCK/R26^Tax, and ORP4L^cko;LCK/R26^Tax mice. (G) Kaplan-Meier comparative survival analysis of WT, LCK/R26^Tax, and ORP4L^cko;LCK/R26^Tax mice (n = 12 mice of each group, log-rank test). (H) Representative images of peripheral blood smears from sick LCK/R26^Tax mice and WT or ORP4L^cko;LCK/R26^Tax littermate mice. Morphologically abnormal leukemic cells with large nuclei were present. The number of abnormal lymphocytes on the smears from each cohort are shown. Scale bars, 100 μm. (I) The percentage of CD3⁺CD4⁺, CD4⁺CD8⁺, CD44⁺CD25⁺, and CD3⁺c-kit⁺ cells in the peripheral blood of sick LCK/R26^Tax mice and WT or ORP4L^cko;LCK/R26^Tax littermate mice. Mean ± standard deviation (SD; n = 7 mice of each group; Student t test). (J-K) Splenomegaly (J) and hepatomegaly (K) in sick LCK/R26^Tax mice and WT or ORP4L^cko;LCK/R26^Tax littermate mice. Representative histologic hematoxylin and hematoxylin eosin–stained sections show T-cell infiltration and immunohistochemical images with positive CD3-specific antibody staining. Scale bars, 100 μm. Mean ± SD (n = 7 mice of each group; Student t test). *P < .05; ***P < .001.