Necdin-null hematopoietic cells are highly sensitive to chemotherapy. (A) Survival after weekly 5-FU administration. 5-FU was administered intraperitoneally weekly (the initial dose was 125 mg/kg, with subsequent doses of 90 mg/kg) and the survival rates of mice repopulated with wild-type (WT) or necdin-null (Ndn null) fetal liver cells were measured. Results were analyzed with a log-rank nonparametric test and expressed as Kaplan-Meier survival curves (P = .0387, n = 10). (B) Hematopoietic reconstitution was monitored by serial peripheral blood count of mice injected with a single dose of 5-FU (200 mg/kg intraperitoneally). WBC counts are shown at each point after 5-FU administration as a percentage of the initial values for each group of mice (mean ± SD; n = 3 for each time point). (C) Gross morphology of femurs from untreated mice and mice 14 days after 5-FU administration is shown. Slides were stained with H&E. The slides were analyzed under a Zeiss Axioplan 2 Upright Wide-field Microscope (Carl Zeiss) equipped with a Zeiss AxiCam HRc Camera (Carl Zeiss; original magnification ×100 with a 10× objective). The images were acquired by a Volocity software (PerkinElmer). (D) HSCs isolated from the mice repopulated with wild-type or necdin-null fetal liver cells were assessed for apoptosis 60 hours after a dose of 5-FU (200 mg/kg intraperitoneally) using DAPI and annexin V staining. Data shown are mean percentage (± SD) of annexin V⁺/DAPI⁻ Lin⁻Sca-1⁺c-Kit⁺CD48⁻CD150⁺ cells (P = .015, n = 5). (E) The proliferation of Lin⁻Sca-1⁺c-Kit⁺CD48⁻CD150⁺ cells isolated from mice reconstituted with wild-type or necdin-null fetal liver cells 4 days after 5-FU administration was measured by BrdU incorporation in vivo over 48 hours (P = .76, n = 5).