title: Fancb deficiency impairs hematopoietic stem cell function.
abstract: Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, variable congenital malformations and a predisposition to malignancies. FANCB (also known as FAAP95), is the only X-linked FA gene discovered thus far. In the present study, we investigated hematopoiesis in adult Fancb deficient (Fancb(-/y)) mice and found that Fancb(-/y) mice have decreased hematopoietic stem cell (HSC) quiescence accompanied by reduced progenitor activity in vitro and reduced repopulating capacity in vivo. Like other FA mouse models previously reported, the hematopoietic system of Fancb(-/y) mice is hypersensitive to DNA cross-linking agent mitomycin C (MMC), which induces bone marrow failure in Fancb(-/y) mice. Furthermore, Fancb(-/y) BM exhibits slower recovery kinetics and less tolerance to myelotoxic stress induced by 5-fluorouracil than wild-type littermates. RNA-seq analysis reveals altered expression of genes involved in HSC function and cell cycle regulation in Fancb(-/y) HSC and progenitor cells. Thus, this Fancb(-/y) mouse model provides a novel approach for studying the critical role of the FA pathway not only in germ cell development but also in the maintenance of HSC function.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.|Divisions of Radiation Health, College of Pharmacy, UAMS.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Surya
authors.initials: S
authors.lastname: Amarachintha
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Erden
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229.
authors.forename: Amom Ruhikanta
authors.initials: AR
authors.lastname: Meetei
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Andreassen
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229.|Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Satoshi H
authors.initials: SH
authors.lastname: Namekawa
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229.
authors.forename: Qishen
authors.initials: Q
authors.lastname: Pang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001772:Blood Cell Count; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005199:Fanconi Anemia / Q000097:blood / Q000235:genetics / Q000473:pathology; D051856:Fanconi Anemia Complementation Group Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016685:Mitomycin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C000607976:FANCB protein, mouse; D051856:Fanconi Anemia Complementation Group Proteins; D016685:Mitomycin; D005472:Fluorouracil