Alox15 mice exhibit primary defect in HSC function. (A) The hematopoietic compartment derived from Alox15 BM in competitive reconstitution assay is defective. Lethally irradiated congenic B6.SJL mice were reconstituted with a 9:1 ratio of B6 (▴) or Alox15 (□) (CD45.2, test) BM cells to B6.SJL (CD45.1, competitor) BM cells. Reconstitution was monitored by quantifying the percentage of donor-derived CD45.2⁺ blood cells in recipients using flow cytometry at the indicated times. The percentage of CD45.2⁺ total leukocytes (CD45⁺ cells), CD3⁺ cells, B220⁺ cells, and Mac1⁺Gr1⁺ is depicted; **P < .01. (B) Reduction in Alox15 LT-HSC following during competitive reconstitution. At 16 weeks after engraftment, the percentage of B6 and Alox15 CD45.2 donor-derived Flt3⁻LSK and Flt3⁺LSK in 9:1 competitively reconstituted mice was determined by flow cytometry (n = 6). (C) Hematopoietic subsets in B6 and Alox15 E14.5 fetal livers analyzed by flow cytometry. (D-E) HSC-derived from Alox15 fetal livers are functionally defective. Analysis of hematopoietic reconstitution of lethally irradiated congenic mice at indicated times after engraftment of B6 or Alox15 E14.5 fetal liver cells mixed 2:1 with congenic competitor BM cells. (D) CD45.2⁺ WBC subsets were determined by flow cytometry. (E) Indicated progenitor populations in BM harvested 16 weeks after transfer were analyzed for CD45.2⁺ cells. Both percentage and absolute number of B6 and Alox15-derived cells are shown (n = 5); *P < .05, **P < .01. All error bars represent mean (± SEM).