Fanca ^−/− Aldh9a1 ^−/− mouse model shows mild hematopoietic phenotypes and increased solid tumor incidence with aging. (A) Relative weight among same-sex littermates. Earliest available weight record was used once in lifetime per mouse between 6 and 10 wk of age and normalized to that of same-sex dKO littermates (dKO n = 19; other genotypes n = 46). An unpaired two-sided t test was performed (****, P < 0.0001). The red line denotes a mean value for each condition. (B) Number of mice with and without eye abnormalities (corneal opacity, microphthalmia, and anophthalmia). Data from Fanca KO and dKO mice are shown (two-sided Chi-square test; P = 0.0782). None of the WT and Aldh9a1 KO mice had eye abnormalities. (Number of mice examined: WT n = 53, Aldh9a1 KO n = 87, Fanca KO n = 27, and dKO n = 50). (C) Kaplan–Meier survival curve of four genotype groups. Log-rank test was performed comparing genotypes (**, P = 0.0073). (D–I) Bone marrow aspiration was performed in mice of 8 to 12 wk of age. Frequency of LT-HSC (E), ST-HSC (F), LSK (G), LK (H), and MEP (I) of live single cells from fresh bone marrow aspirate samples (WT n = 14, Aldh9a1 KO n = 12, Fanca KO n = 13, and dKO n = 13). One-way ANOVA followed by Tukey’s multiple comparison test was performed (ns, not significant; *, P < 0.05; **, P < 0.005; ***, P < 0.0005;****, P < 0.0001). Error bars, SD. LT-HSC, long-term HSC; ST-HSC, short-term HSC; LSK, linage-negative/Sca-1–positive/cKit-high population; LK, lineage-negative/cKit-high population; MEP, megakaryocyte-erythroid progenitor. (I) Quantification of mice with and without all types of tumors on complete necropsies at 18–24 mo of age. Both sexes were included in this analysis. Chi-squared test was performed between groups (*, P < 0.05; **, P < 0.005). All tumor data are included in Table S3. (J) Quantification of female mice with and without ovarian tumors identified during complete necropsy at 18–24 mo of age. Chi-squared test was performed between groups (*, P < 0.05; **, P < 0.005). dKO, double KO (Fanca^−/−Aldh9a1^−/−).