The major histocompatibility complex (MHC) of mammals (H-2 in mice; HLA in humans) is a multigene family whose members encode cell - surface glycoproteins. Recently, attention has been. focused on possible non-immune functions of MHC associated genes. It is known that there are one or more major genes associated with the H-2 complex that influence pre- and post-implantation development including timing of the first cleavage division, steroid receptor number and responsiveness, morphogenesis of the mandible and other facial structures and overall fetal growth and survival. Variation in all of these traits is related to variation in H-2 haplotype. Preliminary studies in our laboratory suggests that the same is true of normal lung development. Given this, we will use morphometric assays, along with specific breeding schemes and data analyses to determine (a) the degree of association of lung development with H-2 haplotype, (b) the existence of maternal effects (genotype cytoplasmic, etc.), and (c) the proportion of the total phenotypic variation among congenic strains that is due to environmental variation. Further, we will use monoclonal antibodies to determine if the specific spatiotemporal patterns of H-2 localization are the same or different in developing lungs of congenic mice with differing haplotypes. Since corticosteroids are known to accelerate lung development, we will repeat all experiments after maternal treatment with same.
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