Perivascular infiltrations and lymphoid tissue disruption resulting from abnormal myeloid dissemination and increased myelopoiesis in hypoallelic mice. Hematoxylin and eosin-stained paraffin sections of spleen (A-B) and liver (C-D). Spleen from a healthy littermate (A) and an MDS/MPN NR4A1^+/−NR4A3^−/− mouse (at 6 months; B) revealed loss of distinct splenic architecture, including well-defined red and white pulp. Histologic analysis of livers from a healthy littermate (C) and an MDS/MPN NR4A1^+/−NR4A3^−/− mouse (at 6 months) (D) showed large regions of perivascular infiltration. Scale bar represents 50 μm (60×/1.25 objective magnification). (E-H) Antimyeloperoxidase immunohistochemistry revealed myeloid contribution to infiltrates in the liver (F) and spleen (H). These infiltrates were not present in control liver (E) or spleen (G). Scale bars represent 50 μm. (I-J) Representative dot plots from flow cytometric analysis of BM and spleen (SP) demonstrate an increase in myeloid cells (CD11b⁺/Gr-1⁻ and CD11b⁺/Gr-1⁺) in diseased mice compared with healthy littermates (I). A decrease in the percentage of B-lymphocytes (B220⁺/CD19⁺) was also noted in diseased mice compared with healthy littermates (J). Numbers shown are the average percentage of total cells for the associated region (averaged from n = 4 mice per genotype; age range, 9-12 months).