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Phenotypes Associated with This Genotype
Genotype
MGI:3698734
Allelic
Composition
Zap70m1Saka/Zap70m1Saka
Genetic
Background
involves: BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zap70m1Saka mutation (0 available); any Zap70 mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• proliferative response to various T cell stimulating treatments is reduced compared to controls (J:86607)
• poor proliferative responses to TCR and CD28 stimulation (J:154166)
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• however, total thymic cellularity is only mildly decreased
• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells
• TCRhigh mature thymocytes are decreased in number and ratio compared to wild-type, while TCRlow immature cells increase in thymus
• thmocytes exhibit abnormal sensitivity to both positive and negative selection
• defective clonal deletion of Vbeta5 and Vbeta11 thymocytes from endogenous viral superantigens, Mtv-8 and Mtv-9
• mice show positive thymic selection of arthritogenic autoimmune T cells (J:86607)
• numbers of the HSAlo TCRbetahi cells are substantially decreased in mutant mice as compared with thymocytes from wild-type mice (J:154166)
• B cell numbers are relatively increased
• peripheral CD4+ numbers are decreased, with relative increase in B cells (J:86607)
• absolute numbers of CD4 single positive thymocytes are profoundly reduced, and fewer mature CD4+ T cells are present in the periphery (J:154166)
• peripheral CD8+ numbers are decreased, with relative increase in B cells (J:86607)
• absolute numbers of CD8 single positive thymocytes are profoundly reduced, and fewer mature CD8+ T cells are present in the periphery (J:154166)
• increase percentages of memory CD4 + T cells
• a marked reduction in both thymic T reg cell frequency as well as absolute T reg cell numbers
• the percentages of CD45RBlo CD4+ T cells were increased
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• mice display severe hypergammaglobulinemia

cellular
• proliferative response to various T cell stimulating treatments is reduced compared to controls (J:86607)
• poor proliferative responses to TCR and CD28 stimulation (J:154166)

immune system
• proliferative response to various T cell stimulating treatments is reduced compared to controls (J:86607)
• poor proliferative responses to TCR and CD28 stimulation (J:154166)
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• however, total thymic cellularity is only mildly decreased
• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells
• TCRhigh mature thymocytes are decreased in number and ratio compared to wild-type, while TCRlow immature cells increase in thymus
• thmocytes exhibit abnormal sensitivity to both positive and negative selection
• defective clonal deletion of Vbeta5 and Vbeta11 thymocytes from endogenous viral superantigens, Mtv-8 and Mtv-9
• mice show positive thymic selection of arthritogenic autoimmune T cells (J:86607)
• numbers of the HSAlo TCRbetahi cells are substantially decreased in mutant mice as compared with thymocytes from wild-type mice (J:154166)
• B cell numbers are relatively increased
• peripheral CD4+ numbers are decreased, with relative increase in B cells (J:86607)
• absolute numbers of CD4 single positive thymocytes are profoundly reduced, and fewer mature CD4+ T cells are present in the periphery (J:154166)
• peripheral CD8+ numbers are decreased, with relative increase in B cells (J:86607)
• absolute numbers of CD8 single positive thymocytes are profoundly reduced, and fewer mature CD8+ T cells are present in the periphery (J:154166)
• increase percentages of memory CD4 + T cells
• a marked reduction in both thymic T reg cell frequency as well as absolute T reg cell numbers
• the percentages of CD45RBlo CD4+ T cells were increased
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• mice display severe hypergammaglobulinemia
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• the percentages of IL-17 producing cells are 15- fold higher than in the wild-type controls
• IL-2 production after CD3 stimulation was greatly reduced in mutant mice
• mice develop Rheumatoid Factor antibodies after zymosan challenge
• mice develop high titres of rheumatoid factor, autoantibodies to type II collagen, heat shock protein-70 and high levels of circulating immune complexes
• by ~2 months of age
• swollen joints showed severe synovitis with subsynovial neutrophil, lymphocyte, macrophage and plasma cell infiltration
• pneumonitis with perivascular and peribronchiolar cellular infiltration (extra-articular manifestation of arthritis) affects >90% of mutants by 6 months of age

skeleton
• mice develop Rheumatoid Factor antibodies after zymosan challenge
• by ~2 months of age
• swollen joints showed severe synovitis with subsynovial neutrophil, lymphocyte, macrophage and plasma cell infiltration
• by 8-12 months of age
• at 8-12 months of age, fusion of subchondral bones (wrist and ankle joints) is observed radiographically
• dislocation of wrist and ankle joints is observed radiographically at 8-12 months of age
• swelling with hyperaemia is evident at 2 month of age at interphalangeal joints of forepaws, then proceeding symmetrically to other finger joints of fore- and hindpaws and wrists and ankles
• severe synovitis with inflammatory cell infiltration is observed in swollen joints, and increases in severity with age

respiratory system
• pneumonitis with perivascular and peribronchiolar cellular infiltration (extra-articular manifestation of arthritis) affects >90% of mutants by 6 months of age

integument
• >90% of mice show infiltration of inflammatory cells to skin by 6 months of age

endocrine/exocrine glands
• significant decrease in the absolute number of CD4 and CD8 single positive subsets
• however, total thymic cellularity is only mildly decreased
• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
rheumatoid arthritis DOID:7148 OMIM:180300
J:86607


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
04/16/2019
MGI 6.13
The Jackson Laboratory