Transgenic Expression of the Activating Natural Killer Receptor Ly49H Confers Resistance to Cytomegalovirus in Genetically Susceptible Mice

• DOI: 10.1084/jem.20021713
• Publication Date: 2003-02-18T19:28:50Z
• Authors: Seung-Hwan Lee; Ahmed Zafer; Yves de Repentigny; Rashmi Kothary; Michel L. Tremblay; Philippe Gros; Pascale Duplay; John R. Webb; Silvia M. Vidal
• Keywords: Transgenesis; Bacterial artificial chromosome

Natural resistance to infection with mouse cytomegalovirus (MCMV) is controlled by a dominant locus, Cmv1. Cmv1 linked the Ly49 family of natural killer receptors on distal chromosome 6. While some studies localized as gene cluster, genetic and functional analysis identified Ly49h pivotal factor in MCMV. The role these two independent genomic domains MCMV was evaluated complementation using transgenesis bacterial artificial chromosomes (BAC) genetically susceptible mice. Phenotypic characterization transgenic animals traced single region spanning gene. appearance Ly49H protein NK cells mice coincided emergence resistance, there threshold level associated full recovery. Finally, expression context either susceptibility alleles, Cmv1sBALB or Cmv1sFVB, conferred infection. These results demonstrate that necessary sufficient confer formally allelism between Ly49h. This panel provides unique resource study possible pleiotropic effect