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...

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Bibliographic Details
Published in:Immunogenetics (New York) 2007-11, Vol.59 (11), p.853-859
Main Authors: Konno, Akihiro, Takiguchi, Mitsuyoshi, Takada, Kensuke, Usami, Takeshi, Azumi, Kaoru, Kubota, Hisayo, Inaba, Mutsumi, Saegusa, Junzo, Kon, Yasuhiro
Format: Article
Language:English
Subjects:
Animals
B cell
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Cell growth
Chromosome Mapping
Crosses, Genetic
Disease Models, Animal
Female
Gene mapping
Genes, Recessive
Genotype
Humans
Immunology
Infiltration
IQI mouse
Lesions
Male
Mice
Mice, Inbred C57BL
Phenotype
QTL
Quantitative Trait Loci
Sialadenitis - genetics
Sialadenitis - immunology
Sialadenitis - pathology
Sialitis
Sjogren's Syndrome - genetics
Sjogren's Syndrome - immunology
Sjogren's Syndrome - pathology
Sjögren's syndrome
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Summary: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.
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-007-0244-4