title: Aberrant development of thymocytes in mice lacking laminin-2.
abstract: In previous in vitro studies, we proposed a role for the extracellular matrix component, laminin-2, and its integrin receptor, VLA-6, in thymocyte development. The characterization of two dystrophic mouse strains with different defects in laminin-2 allowed us to examine this proposal in vivo. Mice deficient in laminin-2, dy/dy, show a significant reduction in thymus size and number of thymocytes compared to normal littermates. These mice also exhibited apparent alterations of thymic architecture. Examination of the CD4/CD8 populations in dy/dy thymi showed large relative increases in the DN (CD4- CD8-) and SP (CD4+ CD8-, CD4- CD8+) populations and a significant decrease in the DP (CD4+ CD8+) population. Further examination of the DN population for CD44 and CD25 expression showed a remarkable decrease in the more mature pre-T cell populations. Analysis of apoptosis in situ, and by flow cytometry, in dy/dy thymi revealed a significant increase in apoptotic DN thymocytes in the capsule and subcapsular regions. Interestingly, thymocyte development appeared to proceed normally in dystrophic mice expressing a mutant form of laminin-2, dy2J, as well as, in fetal and neonatal dy/dy mice. We propose that laminin-2 plays an active role in thymocyte development by delivering cell survival and differentiation signals at specific stages of development in young adult mice.
authors.affiliation: Laboratory of Allergic Diseases, NIAID, NIH, Rockville, MD 20852-1727, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Magner
authors.forename: A C
authors.initials: AC
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Owens
authors.forename: M J
authors.initials: MJ
authors.lastname: Hong
authors.forename: A
authors.initials: A
authors.lastname: Brooks
authors.forename: J E
authors.initials: JE
authors.lastname: Coligan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D005260:Female; D005434:Flow Cytometry; D039121:Integrin alpha6beta1; D016023:Integrins / Q000502:physiology; D007797:Laminin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009136:Muscular Dystrophies / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin