Mouse Genome Informatics
tg
    Tg(Tnfsf13b)1Fma/0
B6.Cg-Tg(Tnfsf13b)1Fma
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
hematopoietic system
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
• presence of B-1a (CD5+) B cells are detected compared to controls
• a 3-fold increase in B-1b (CD5-) B cells
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations (mutants 45.5% vs wild-type 14.4%)
• B220hi/IgMhi B cell subset is greatly increased in transgenic mice
• IgM dull subset of B cells is larger in transgenic mice compared to control
• large IgMhi B cell subset is phenotypically different from the small IgMhi B cell subset in controls, resembling marginal zone B cells
• numerous germinal centers are observed in B cell follicles of young transgenic mice compared to wild-type and aged transgenic mice
• splenic marginal zone is increased in size, particularly notable in aged mice
• mice exhibit elevated levels in both steady state and in response to antigen stimulation; at 12 weeks of age, IgA levels are increased 1500-fold over wild-type (22.7 mg/ml IgA vs 0.015 mg/ml in wild-type - hyper-IgA)
• augmented IgA staining is found in lamina propria of transgenic mice

immune system
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates
• a marked increase in some B cell subsets compared to wild-type is detected in 12 week old mice
• there is an increased frequency of B220neg/lo, IgA+ plasma cells in lamina propria preparations (mutants 45.5% vs wild-type 14.4%)
• IgM dull subset of B cells is larger in transgenic mice compared to control
• B220hi/IgMhi B cell subset is greatly increased in transgenic mice
• large IgMhi B cell subset is phenotypically different from the small IgMhi B cell subset in controls, resembling marginal zone B cells
• presence of B-1a (CD5+) B cells are detected compared to controls
• a 3-fold increase in B-1b (CD5-) B cells
• numerous germinal centers are observed in B cell follicles of young transgenic mice compared to wild-type and aged transgenic mice
• splenic marginal zone is increased in size, particularly notable in aged mice
• mice exhibit elevated levels in both steady state and in response to antigen stimulation; at 12 weeks of age, IgA levels are increased 1500-fold over wild-type (22.7 mg/ml IgA vs 0.015 mg/ml in wild-type - hyper-IgA)
• augmented IgA staining is found in lamina propria of transgenic mice
• most mice over 13 months of age show signs of severe nephritis

renal/urinary system
• proteinuria is detected only in a subset of 8-month old mice
• most mice over 13 months of age show signs of severe nephritis
• IgA immune complexes are detected in majority of young and aged mice
• IgA deposits are found in nearly all glomeruli, while deposits of each IgG, and IgM are also detected, while very little Ig deposition is found in wild-type kidneys
• significant IgA deposits are found specifically in kidney glomerular mesangium
• in 8-month old mice, glomeruli are slightly enlarged and hypercellular

homeostasis/metabolism
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
• proteinuria is detected only in a subset of 8-month old mice

digestive/alimentary system
• many mice over 13 months of age have enlarged salivary glands
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates

endocrine/exocrine glands
• many mice over 13 months of age have enlarged salivary glands
• mice aged 12-15.5 months of age produce significantly less saliva compared to age-matched controls; this difference is not observed in mice aged 8-10 months
• 60% of mice over 12 months of age have severely inflamed salivary glands with large leukocytic infiltrates

tumorigenesis
• some mice (3 cases) have large submaxillary tumors which contain hyperplastic lymphoid tissue composed of activated B cells and numerous germinal centers; these abnormal aggregates of B lymphoid cells are found in lymphocytic infiltrates of some tumor-free mice

Mouse Models of Human Disease
OMIM IDRef(s)
Sjogren Syndrome 270150 J:73711