Identification of a quantitative trait locus regulating B cell-dominant infiltration into autoimmune sialitis lesions of the IQI mouse model of primary Sjögren's syndrome.
Sjögren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p = 0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.
Konno
Akihiro
A
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. akonno@vetmed.hokudai.ac.jp
Takiguchi
Mitsuyoshi
M
Takada
Kensuke
K
Usami
Takeshi
T
Azumi
Kaoru
K
Kubota
Hisayo
H
Inaba
Mutsumi
M
Saegusa
Junzo
J
Kon
Yasuhiro
Y
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D040641:Quantitative Trait Loci; D012793:Sialadenitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology* / Q000473:pathology