title: Auto-antibody production and glomerulonephritis in congenic Slamf1-/- and Slamf2-/- [B6.129] but not in Slamf1-/- and Slamf2-/- [BALB/c.129] mice.
abstract: Several genes in an interval of human and mouse chromosome 1 are associated with a predisposition for systemic lupus erythematosus. Congenic mouse strains that contain a 129-derived genomic segment, which is embedded in the B6 genome, develop lupus because of epistatic interactions between the 129-derived and B6 genes, e.g. in B6.129chr1b mice. If a gene that is located on chromosome 1 is altered through homologous recombination in 129-derived embryonic stem cells (ES cells) and if the resultant knockout mouse is backcrossed with B6, interpretation of the phenotype of the mutant mouse may be affected by epistatic interactions between the 129 and B6 genomes. Here, we report that knockout mice of two adjacent chromosome 1 genes, Slamf1(-/-) and Slamf2(-/-), which were generated with the same 129-derived ES cell line, develop features of lupus, if backcrossed on to the B6 genetic background. By contrast, Slamf1(-/-) [BALB/c.129] and Slamf2(-/-) [BALB/c.129] do not develop disease. Surprisingly, Slamf1(-/-) [B6.129] mice develop both auto-antibodies and glomerulonephritis between 3 and 6 months of age, while disease fully develops in Slamf1(-/-) [B6.129] mice after 9-14 months. Functional analyses of CD4(+) T cells reveals that Slamf2(-/-) T cells are resistant to tolerance induction in vivo. We conclude that the Slamf2(-/-) mutation may have a unique influence on T-cell tolerance and lupus.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. mkeszei@bidmc.harvard.edu
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.forename: Yvette E
authors.initials: YE
authors.lastname: Latchman
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Vanguri
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Brown
authors.forename: Cynthia
authors.initials: C
authors.lastname: Detre
authors.forename: Massimo
authors.initials: M
authors.lastname: Morra
authors.forename: Carolina V
authors.initials: CV
authors.lastname: Arancibia-Carcamo
authors.forename: Carolina V
authors.initials: CV
authors.lastname: Arancibia
authors.forename: Elahna
authors.initials: E
authors.lastname: Paul
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.forename: Wilson
authors.initials: W
authors.lastname: Castro
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007178:Inbreeding; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D057507:Mice, 129 Strain; D020297:Mice, Congenic; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C000604062:Slamf1 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1