Characterization of xeroderma pigmentosum group G bone marrow chimera mice

抄録

In addition to xeroderma pigmentosum (XP), mutations in the human XPG gene cause early onset of Cockayne syndrome (CS) in some patients with characteristics such as growth retardation and short life span. Xpg null mice exhibited the same characteristics as human patients do. We generated four mutant Xpg mouse strains with different mutations in Xpg gene to identify the Xpg region that causes onset of the CS phenotype. We found that the deletion of C terminal 183 amino acids results in the CS phenotype. The primary embryonic fibroblasts isolated from Xpg-deficient mice underwent premature senescence and exhibited the early onset of immortalization. If chimera mice in which some tissues are replaced with Xpg-deficient cells or tissues could be generated, it seems to be very interesting to analyze the fate of such chimera mice and/or Xpg-deficient cells in such chimera mice. So we have generated bone marrow chimera mice in which normal blood cells were replaced with Xpg-deficient cells and examined their life span, shortening of life span by X-irradiation and class switching of immunoglobulin heavy chain. The life span of Xpg-chimera mice was not different from that of normal chimera mice. The life span of Xpg-chimera mice irradiated with X rays was shorter than that of normal chimera mice. Though in vitro studies indicate that Xpg functions as a nuclease for class switching of immunoglobulin heavy chain, class switching was normal even in Xpg-chimera mice.