title: An NZW-derived interval on chromosome 7 moderates sialadenitis, but not insulitis in congenic nonobese diabetic mice.
abstract: Autoimmune lymphocytic infiltration of the salivary glands, termed sialadenitis, is a pathologic feature of Sjögren's syndrome (SjS) that is also prominent in nonobese diabetic (NOD) mice. Genetic factors regulate sialadenitis, and a previous (NOD x NZW)F2 study detected linkage to murine chromosome (Chr) 7. The locus, subsequently annotated as Ssial3, maps to the distal end of Chr7 and overlaps a region associated with type 1 diabetes susceptibility in NOD mice. To examine whether Ssial3 could contribute to both diseases, or was specific for SjS, we generated a congenic mouse strain that harbored an NZW-derived Chr7 interval on the NOD genetic background. This congenic strain exhibited reduced sialadenitis compared with NOD mice and confirmed Ssial3. This reduction, however, did not ameliorate saliva abnormalities associated with SjS-like disease in NOD mice, nor were congenic mice protected against insulitis (lymphocytic infiltration of the pancreatic islets) or diabetes onset. Thus, the Ssial3 locus appears to have a tissue-specific effect for which the NZW allele is unable to prevent other autoimmune traits in the NOD mouse. Anomalous increases for antinuclear Ab production and frequency of marginal-zone B cells were also identified in congenic mice, indicating that the NZW-derived Chr7 interval has a complex effect on the NOD immune system.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Burt
authors.forename: Laura
authors.initials: L
authors.lastname: Watkins
authors.forename: Iris K L
authors.initials: IK
authors.lastname: Tan
authors.forename: Nancy
authors.initials: N
authors.lastname: Wang
authors.forename: Fiona
authors.initials: F
authors.lastname: Quirk
authors.forename: Leanne
authors.initials: L
authors.lastname: Mackin
authors.forename: Phillip
authors.initials: P
authors.lastname: Morgan
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Berzins
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Brodnicki
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000473:pathology; D002874:Chromosome Mapping; D002875:Chromosomes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D012793:Sialadenitis / Q000235:genetics*
chemical_list: D000974:Antibodies, Antinuclear