ABSTRACTWe examine the proliferation and differentiation of bone marrow (BM) progenitors from inbred Rocky Mountain White (IRW) mice, a strain used primarily for retrovirus infection studies. In contrast to findings with BALB/c and C57BL/6 strains, IRW BM cells cannot proliferate or generate pure eosinophil cultures ex vivo in response to a defined cytokine regimen. Analysis of IRW BM at baseline was unremarkable, including 0.08 ± 0.03% Lin–Sca-1+c-kit+ (LSK) hematopoietic stem cells and 5.2 ± 0.3% eosinophils; the percentage of eosinophil progenitors (EoPs; Lin–Sca-1–c-kit+CD34+IL-5Rα+) was similar in all three mouse strains. Transcripts encoding GM-CSFRα and the IL-3/IL-5/GM-CSF common β chain were detected at equivalent levels in IRW and BALB/c BM, whereas expression of transcripts encoding IL-5Rα, IL-3Rα, and GATA-2 was diminished in IRW BM compared with BALB/c. Expression of membrane-bound IL-5Rα and intracellular STAT5 proteins was also diminished in IRW BM cells. Diminished expression of transcripts encoding IL-5Rα and GATA-2 and immunoreactive STAT5 in IRW BM persisted after 4 days in culture, along with diminished expression of GATA-1. Western blot revealed that cells from IRW BM overexpress nonsignaling soluble IL-5Rα protein. Interestingly, OVA sensitization and challenge resulted in BM and airway eosinophilia in IRW mice; however, the responses were significantly blunted. These results suggest that IRW mice have diminished capacity to generate eosinophils in culture and in vivo, likely as a result of diminished signaling via IL-5Rα.