title: ZASC1 knockout mice exhibit an early bone marrow-specific defect in murine leukemia virus replication.
abstract: BACKGROUND
  ZASC1 is a zinc finger-containing transcription factor that was previously shown to bind to specific DNA binding sites in the Moloney murine leukemia virus (Mo-MuLV) promoter and is required for efficient viral mRNA transcription (J. Virol. 84:7473-7483, 2010).
  
  
  METHODS
  To determine whether this cellular factor influences Mo-MuLV replication and viral disease pathogenesis in vivo, we generated a ZASC1 knockout mouse model and completed both early infection and long term disease pathogenesis studies.
  
  
  RESULTS
  Mice lacking ZASC1 were born at the expected Mendelian ratio and showed no obvious physical or behavioral defects. Analysis of bone marrow samples revealed a specific increase in a common myeloid progenitor cell population in ZASC1-deficient mice, a result that is of considerable interest because osteoclasts derived from the myeloid lineage are among the first bone marrow cells infected by Mo-MuLV (J. Virol. 73: 1617-1623, 1999). Indeed, Mo-MuLV infection of neonatal mice revealed that ZASC1 is required for efficient early virus replication in the bone marrow, but not in the thymus or spleen. However, the absence of ZASC1 did not influence the timing of subsequent tumor progression or the types of tumors resulting from virus infection.
  
  
  CONCLUSIONS
  These studies have revealed that ZASC1 is important for myeloid cell differentiation in the bone marrow compartment and that this cellular factor is required for efficient Mo-MuLV replication in this tissue at an early time point post-infection.
authors.affiliation: Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Seidel
authors.forename: James
authors.initials: J
authors.lastname: Bruce
authors.forename: Mathias
authors.initials: M
authors.lastname: Leblanc
authors.forename: Kuo-Fen
authors.initials: KF
authors.lastname: Lee
authors.forename: Hung
authors.initials: H
authors.lastname: Fan
authors.forename: Paul
authors.initials: P
authors.lastname: Ahlquist
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000821:virology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007942:Leukemia, Experimental / Q000821:virology*; D051379:Mice; D018345:Mice, Knockout; D008979:Moloney murine leukemia virus / Q000502:physiology*; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D012192:Retroviridae Infections / Q000821:virology*; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C585770:ZNF639 protein, mouse