title: Thymic alterations in GM2 gangliosidoses model mice.
abstract: BACKGROUND
  Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies.
  
  
  RESULTS
  In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice.
  
  
  CONCLUSIONS
  These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13.
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Kojima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Koumitsu
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Michiko
authors.initials: M
authors.lastname: Ehara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirayasu
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamanaka
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001284:Atrophy / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D054382:Chemokine CXCL13 / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D020143:Gangliosidoses, GM2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007223:Infant; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000172:deficiency / Q000378:metabolism; D012497:Sandhoff Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D054821:beta-Hexosaminidase beta Chain / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D054382:Chemokine CXCL13; D012333:RNA, Messenger; D017452:Receptors, IgG; D054821:beta-Hexosaminidase beta Chain