Disruption of differentiated functions during viral infection in vivo - V.Mapping of a locus involved in susceptibility of mice to growth hormone deficiency due to persistent lymphocytic choriomeningitis virus infection

Lymphocytic choriomeningitis virus (LCMV) Armstrong strain selectively and persistently infects the majority of growth hormone (GH) producing cells in the anterior lobe of pituitary glands of C3H/St mice but negligibly infect s GH producing cells of BALB/WEHI mice (Oldstone et al., Virology 142, 175- 182, 1985; Oldstone et al., Science 218, 1125-1127 1982). Although infected GH cells remain free of structural damage, disrupted initiation of GH tran scription (Klavinskis and Oldstone, J. Gen. Virol. 68, 1867-1873, 1989; Val samakis et ai., Virology 156, 214-220, 1987) occurs with a resultant decrea se in the synthesis of GH, leading to a failure of growth and development ( Oldstone et al., Science 218, 1125-1127, 1982). Microsatellite mapping of D NA obtained from 101 individual C3H/St x BALB/WEHI F1 ic F1 mice shows that the growth failure correlates with host genes linked (P value 0.0008) on c hromosome 17 just outside of the H-2D MHC site between D17 Mit24 and D17 Mi t51, a distance of 2.5 cM. The genetic mapping done here excludes alpha-dys troglycan (alpha -DG), a known receptor for LCMV (Cao et al., Science 282, 2079-2081, 1998) in pathogenesis of GH disease, as OI-DG is encoded in the mouse by a gene residing on chromosome 9 (Yotsumoto et al., Hum. Mel. Genet 5, 1259-1267, 1996). (C) 2001 Academic Press.