Mammalian Genome

, Volume 17, Issue 5, pp 398–406

Analysis of the MCMV resistome by ENU mutagenesis

  • Karine Crozat
  • Philippe Georgel
  • Sophie Rutschmann
  • Navjiwan Mann
  • Xin Du
  • Kasper Hoebe
  • Bruce Beutler
Article

DOI: 10.1007/s00335-005-0164-2

Cite this article as:
Crozat, K., Georgel, P., Rutschmann, S. et al. Mamm Genome (2006) 17: 398. doi:10.1007/s00335-005-0164-2

Abstract

The mouse cytomegalovirus (MCMV) resistome is the set of host genes with nonredundant functions in resistance to MCMV infection. By screening 3500 G3 germline mutant mice (∼1750 gamete equivalents), we have identified eight transmissible mutations that create MCMV susceptibility in C57BL/6 mice. Among these, a mutation called Domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (VSV) in vitro. This accessory phenotype was not corrected by type I interferon (IFN), which suggested a defect of the type I IFN pathway. Domino corresponds to a point mutation that alters the DNA binding domain of STAT1, leading to a defect of STAT1 activation. Identification of the Domino mutation demonstrates that an in vivo MCMV susceptibility screen is feasible and illustrates how it can provide insight into the resistome. Moreover, some mutations are far more deleterious than Domino in MCMV-infected mice, consistent with the interpretation that certain protein(s) unrelated to IFN production or signaling are more important than IFNs with regard to their net antiviral effects.

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Karine Crozat
    • 1
  • Philippe Georgel
    • 1
    • 2
  • Sophie Rutschmann
    • 1
  • Navjiwan Mann
    • 1
  • Xin Du
    • 1
  • Kasper Hoebe
    • 1
  • Bruce Beutler
    • 1
  1. 1.Department of ImmunologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Laboratoire d’ImmunoGénetique Moléculaire HumaineFaculté de MédecineStrasbourgFrance

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