Germ cell defects and hematopoietic hypersensitivity to γ-interferon in mice with a targeted disruption of the fanconi anemia C gene

Michael A. Whitney, Gordon Royle, Malcolm J. Low, Michele A. Kelly, Michael K. Axthelm, Carol Reifsteck, Susan Olson, Robert E. Braun, Michael C. Heinrich, R. Keaney Rathbun, Grover C. Bagby, Markus Grompe

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

Fantoni anemia (FA) is an autosomal recessive chromosome instability syndrome characterized by progressive bone marrow (BM) failure, skeletal defects, and increased susceptibility to malignancy. FA cells are hypersensitive to DNA cross-linking agents, oxygen and have cell cycle abnormalities. To develop an animal model of the disease we generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene (fac). Mutant mice had normal neonatal viability and gross morphology, but their cells had the expected chromosome breakage and DNAcross-linker sensitivity. Surprisingly, male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable in the peripheral blood during the first year of life, but the colony forming capacity of marrow progenitor cells was abnormal in vitro in mutant mice. Progenitor cells from fac knock-out mice were hypersensitive to interferon γ. This previously unrecognized phenotype may form the basis for BM failure in human FA.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalBlood
Volume88
Issue number1
StatePublished - Jul 1 1996

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Whitney, M. A., Royle, G., Low, M. J., Kelly, M. A., Axthelm, M. K., Reifsteck, C., Olson, S., Braun, R. E., Heinrich, M. C., Rathbun, R. K., Bagby, G. C., & Grompe, M. (1996). Germ cell defects and hematopoietic hypersensitivity to γ-interferon in mice with a targeted disruption of the fanconi anemia C gene. Blood, 88(1), 49-58.