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. 2020 Apr 27;130(6):2827–2844. doi: 10.1172/JCI126215

Figure 7. Loss of NIPA leads to a BM failure phenotype resembling functional Fanc deficiency.

Figure 7

(A) Kaplan-Meier survival curve of VavWT/WT NipaCKO/CKO and VavTg/WT NipaCKO/CKO mice following regular poly(I:C) treatment dying from BM failure. n = 8 VavWT/WT NipaCKO/CKO, n = 6 VavTg/WT NipaCKO/CKO. (B) Leukocyte counts of VavWT/WT NipaCKO/CKO and VavTg/WT NipaCKO/CKO mice following regular poly(I:C) treatment at death compared with control mice at the same time points. n = 6 Nipa+/+; n = 6 Nipa–/–. (C) Representative H&E staining of BM sections of VavWT/WT NipaCKO/CKO and VavTg/WT NipaCKO/CKO mice following regular poly(I:C) treatment sacrificed when moribund or at end of experiment. Original magnification, ×10. Scale bars: 100 μm. (D) Representative confocal microscopy images of LSK cells isolated from untreated or poly(I:C)-treated (day 56) mice (aged 3–5 months). Cells are stained for FANCD2 (red) and DAPI (blue). Original magnification, ×63. (E) Average fluorescence intensity of FANCD2 staining in the nuclei of untreated and poly(I:C)-treated HSCs. Results were normalized to control cells set to 1. Untreated: n = 48 VavWT/WT NipaCKO/CKO; n = 62 VavTg/WT NipaCKO/CKO. Poly(I:C) +d56: n = 40 Nipa+/+; n = 32 Nipa–/–. (F) Representative IHC staining of NIPA (brown) in BM sections from patients with FA (patients 1 and 2) and RCC with (9 and 10) and without (16, 20, and 26–29) known germline predisposition demonstrates distinct NIPA downregulation (patients 26–29) in approximately 45% of analyzed RCC cases. Control samples (Ctrl 1 and 2) represent IHC NIPA BM sections from adult healthy donors. Original magnification, ×63. Scale bar: 20 μm. (G) Representative immunohistochemical staining of FANCD2 (brown) in BM sections from NIPA-downregulated RCC patients (22, 23, and 26). Control sample (Ctrl 1) represents IHC FANCD2 BM section from an adult healthy donor. Original magnification, ×63. Scale bars: 20 μm. **P < 0.01, ***P < 0.001. A log-rank (Mantel-Cox) test (A) or unpaired 2-tailed Student’s t test (B and E) was used for statistical analyses. Data are presented as mean ± SD. See also Supplemental Figures 13 and 14.