title: Fetal origins of hematopoietic failure in a murine model of Fanconi anemia.
abstract: Hematopoietic failure is the predominant clinical manifestation of Fanconi anemia (FA), a rare, recessively inherited disorder. Mutations in 1 of 15 genes that coordinately function in a complex pathway to maintain DNA integrity also predispose patients to constitutional defects in growth and development. The hematologic manifestations have been considered to reflect the progressive loss of stem cells from the postnatal bone marrow microenvironment. Ethical concerns preclude the study of human hematopoiesis in utero. We report significant late gestational lethality and profound quantitative and qualitative deficiencies in the murine Fancc(-/-) fetal liver hematopoietic stem and progenitor cell pool. Fancc(-/-) fetal liver hematopoietic stem and progenitor cells revealed a significant loss of quiescence and decline in serial repopulating capacity, but no substantial difference in apoptosis or levels of reactive oxygen species. Our studies suggest that compromised hematopoiesis in Fancc(-/-) animals is developmentally programmed and does not arise de novo in bone marrow.
authors: Departments of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
authors: Ashley N
authors: AN
authors: Kamimae-Lanning
authors: Natalya A
authors: NA
authors: Goloviznina
authors: Peter
authors: P
authors: Kurre
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005199:Fanconi Anemia / Q000196:embryology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005260:Female; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011247:Pregnancy
chemical_list: D052218:Fanconi Anemia Complementation Group C Protein