title: Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse.
abstract: BACKGROUND
  Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins.
  
  
  RESULTS
  We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4(+)CD8(+) double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus.
  
  
  CONCLUSIONS
  Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells.
authors.affiliation: Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liou
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Walsh
authors.forename: Arineh R
authors.initials: AR
authors.lastname: Vartanian
authors.forename: Daniel
authors.initials: D
authors.lastname: Beltran-Valero de Bernabe
authors.forename: Megan
authors.initials: M
authors.lastname: Welch
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D049030:Dystroglycans / Q000737:chemistry* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006031:Glycosylation; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism; D051379:Mice; D009975:Orthomyxoviridae / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D000199:Actins; D049030:Dystroglycans