Many mouse chromosomal genes are known which affect the susceptibility of mice to retrovirus-induced neoplastic disease. These genes include endogenous retroviral sequences, mouse cellular genes which facilitate or restrict virus replication, and proto-oncogenes disrupted by viral insertion. We have been using standard classical genetics to identify and map genes involved in these phenomena. In one series of experiments, we obtained a molecular clone of the receptor for the amphotropic MuLV cell surface receptor, and we defined the map location of this gene in the mouse. We have also mapped TRBP, a positive regulator of HIV-1, in man and mouse. In other experiments, we have continued analysis of several crosses involving DBA/2J mice which carry a locus, Rmcf, responsible for resistance to the mink cell focus inducing (MCF) subtype of mouse leukemia viruses. We defined the genetic map location of Rmcf; we identified an additional resistance gene in the M. castaneus parent of these same crosses which maps to Chr 1; we identified two additional factors which contribute to this resistance in M. castaneus; and we are following inheritance of Rmcf in serial backcrosses to M. castaneus which lacks endogenous MCF viruses. These experiments should help determine whether Rmcf represents an endogenous provirus, expression of which blocks viral cell surface receptors, and should characterize the genetic factors responsible for resistance in M. castaneus.

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National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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Yan, Yuhe; Buckler-White, Alicia; Wollenberg, Kurt et al. (2009) Origin, antiviral function and evidence for positive selection of the gammaretrovirus restriction gene Fv1 in the genus Mus. Proc Natl Acad Sci U S A 106:3259-63
Yan, Yuhe; Kozak, Christine A (2008) Novel postentry resistance to AKV ecotropic mouse gammaretroviruses in the African pygmy mouse, Mus minutoides. J Virol 82:6120-9
Yan, Yuhe; Knoper, Ryan C; Kozak, Christine A (2007) Wild mouse variants of envelope genes of xenotropic/polytropic mouse gammaretroviruses and their XPR1 receptors elucidate receptor determinants of virus entry. J Virol 81:10550-7
Tanaka, Kazuhiro; Tsumaki, Noriyuki; Kozak, Christine A et al. (2006) A Kruppel-associated box-zinc finger protein, NT2, represses cell-type-specific promoter activity of the alpha2(XI) collage gene. Mol Cell Biol 26:8215-6
Wu, Tiyun; Yan, Yuhe; Kozak, Christine A (2005) Rmcf2, a xenotropic provirus in the Asian mouse species Mus castaneus, blocks infection by polytropic mouse gammaretroviruses. J Virol 79:9677-84
Lee, Suk Keun; Kim, Yeon Sook; Lee, Sang Shin et al. (2004) Molecular cloning, chromosomal mapping, and characteristic expression in tooth organ of rat and mouse Krox-25. Genomics 83:243-53
Jung, Yong Tae; Wu, Tiyun; Kozak, Christine A (2003) Characterization of recombinant nonecotropic murine leukemia viruses from the wild mouse species Mus spretus. J Virol 77:12773-81
Jung, Yong Tae; Kozak, Christine A (2003) Generation of novel syncytium-inducing and host range variants of ecotropic moloney murine leukemia virus in Mus spicilegus. J Virol 77:5065-72
Denicourt, Catherine; Kozak, Christine A; Rassart, Eric (2003) Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing. J Virol 77:37-44
Carp, R I; Meeker, H C; Chung, R et al. (2002) Murine leukemia virus in organs of senescence-prone and -resistant mouse strains. Mech Ageing Dev 123:575-84

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