Fetal origins of hematopoietic failure in a murine model of Fanconi anemia.

Ashley N. Kamimae-Lanning, Natalya A. Goloviznina, Peter Kurre

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2008-2012
Number of pages5
JournalBlood
Volume121
Issue number11
DOIs
StatePublished - Mar 14 2013

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Fanconi Anemia
Hematopoietic Stem Cells
Liver
Bone
Hematopoiesis
Stem cells
Reactive Oxygen Species
Animals
Genes
Bone Marrow
Apoptosis
Defects
DNA
Growth and Development
Stem Cells
Mutation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Fetal origins of hematopoietic failure in a murine model of Fanconi anemia. / Kamimae-Lanning, Ashley N.; Goloviznina, Natalya A.; Kurre, Peter.

In: Blood, Vol. 121, No. 11, 14.03.2013, p. 2008-2012.

Research output: Contribution to journalArticle

Kamimae-Lanning, Ashley N. ; Goloviznina, Natalya A. ; Kurre, Peter. / Fetal origins of hematopoietic failure in a murine model of Fanconi anemia. In: Blood. 2013 ; Vol. 121, No. 11. pp. 2008-2012.
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