Fig. 2: Overexpression of PRMT5 induces lymphoid proliferation in vivo.

a Schematic representation of the construct used to generate the Eµ-PRMT5 transgenic mouse. RT-qPCR for hPRMT5 in B cells of Eµ-PRMT5 mice and WT littermates. mTbp1 shown as control. Circles indicate individual mice (n = 3, Eµ-PRMT5 mice; n = 2, WT mice). Bars indicate mean ± SD. b Eµ-PRMT5 mice (n = 67) and WT littermates (n = 10) survival. Eµ-PRMT5 mice median survival = 829 days. Kaplan–Meier plot statistics: Mantel–Cox test [P = 0.0004, hazard ratio = 0.12 95% CI (0.069–0.23)]. c Cause of death (COD) observations for Eµ-PRMT5 transgenic mice (n = 75). Categorical COD was recorded as either spontaneous death or meeting predefined euthanasia criteria. Unresolved cause of death cases were grouped as “other”. d A cohort of Eµ-PRMT5 (n = 26), Eµ-TCL1 (n = 35), and WT littermate mice (n = 9) were assessed monthly for spontaneous disease expansion by flow cytometry of peripheral blood. Expansive populations of T cells (Cd45⁺/Cd5⁺), B cells (Cd19⁺/Cd5⁺/B220^bright), CLL-like cells (Cd19⁺/Cd5⁺/B220^dim), or myeloid cells (SSC^high & Cd19⁻/Cd5⁻) were observed in varying ratios within groups. e Rate of CLL-like cell accumulation in Eµ-PRMT5 and WT littermate mice (from d). The dotted line indicates 10% Cd5+ /B220+ cells in the blood observed via flow cytometry. f Histopathology analysis via hematoxylin and eosin (H&E) staining of Eµ-PRMT5 (n = 4) mice at ERC and age-matched WT littermate (n = 3). L anaplastic large lymphocytes, H bland histiocytes, S sheets of small lymphocytes. g Representative immunohistochemistry of tumors from Eµ-PRMT5 (n = 5) mice. Arrows indicate scattered CD3+ and F4/80+ cells. This mixture of cell types is consistent with the diagnosis of histiocyte-associated lymphoma, which is the murine counterpart of the human disease T-cell and Histiocyte-rich B-cell lymphoma. B220 and CD3 shown in spleen, F4/80 shown in liver. Images shown at ×40 magnification. Scale bar is 50 µm. h B-cell receptor variable gene usage in splenic CLL-like cells from Eµ-PRMT5 (n = 4) and Eµ-TCL1 (n = 1) mice evaluated via RNA-seq. Colors indicate BCR gene usage. i Bulk RNA-seq in splenic CLL-like cells from Eµ-PRMT5 (from h) and Eµ-TCL1 mice (n = 3). Red highlighted genes have adjusted P value <0.05 and fold change >4. Source data are provided as a Source Data file.