Recovery from an erythroid-specific stress is delayed in Cul4A heterozygous mice. (A) Twelve Cul4A^+/– and 12 wild-type littermate controls were treated with 50 mg/kg phenylhydrazine on days 0, 1, and 3 (indicated by arrows), and hematocrits were measured at days 0 to 7. The mean (percent ± SEM) for wild-type (□) and Cul4A^+/– (▴) mice are graphed for 2 independent experiments. At day 7, *P = .01. (B) Six Cul4A^+/– and 6 wild-type mice were treated with phenylhydrazine as described in panel A, and bone marrow was isolated at day 5. Total cellularity per femur was determined and the number of erythroid precursors per femur for each mouse was determined (see “Materials and methods”). The means (cells per femur ± SEM) are graphed for the results from 2 independent experiments. *P < .001. (C) For the 6 Cul4A^+/– and 6 wild-type mice described, the number of cells in each of the 4 erythroid precursor populations (described in “Results” and for Figure 1C) was determined, and these results from 2 independent experiments are graphed (mean ± SEM). For proerythroblasts (PROERY), *P < .001. (D) Spleen colony-forming unit (CFU-S) assays were performed by injecting 3 × 10⁴ low-density mononuclear bone marrow cells isolated from 4 wild-type or 4 Cul4A^+/– mice into the tail vein of lethally irradiated adult, female, C57BL/6 recipients (3-4 recipients per wild-type or Cul4A^+/– donor). After 8 days, spleens were removed and fixed in Telly fixative (20 parts 70% ethanol, 1 part glacial acetic acid, 1 part formalin), and the numbers of macroscopic colonies were counted. Means ± SEM for the combined results from 2 independent experiments are graphed. When the results for these 4 Cul4A^+/– and 4 wild-type donors were compared, *P = .005.