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Aberrant Development of Thymocytes in Mice Lacking Laminin-2

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...

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Detalles Bibliográficos
Autores principales: Magner, William J., Chang, Andrew C., Owens, Jennie, Hong, M-J. P., Brooks, Andrew, Coligan, John E.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276047/
https://www.ncbi.nlm.nih.gov/pubmed/11097211
http://dx.doi.org/10.1155/2000/90943
Descripción
Sumario: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, dy(2J), 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.