All Phenotypes Zap70<m1Saka> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Zap70^m1Saka/Zap70^m1Saka	involves: BALB/c	MGI:3698734
ht2	Zap70^m1Saka/Zap70⁺	involves: BALB/c	MGI:3698735
ht3	Zap70^m1Saka/Zap70^tm1Dlo	involves: 129P2/OlaHsd * BALB/c	MGI:3698739
ht4	Zap70^m1Saka/Zap70^tm2.1Weis	involves: 129S4/SvJae * BALB/c	MGI:4399132
cx5	Zap70^m1Saka/Zap70^tm1Dlo Tg(Lck-ZAP70)824Saka/0	involves: 129P2/OlaHsd * BALB/c	MGI:3698747
cx6	Zap70^m1Saka/Zap70^m1Saka Tg(DO11.10)10Dlo/0	involves: BALB/c * C3H * C57BL/6	MGI:3698742
cx7	Zap70^m1Saka/Zap70^m1Saka Tg(TcraH-Y,TcrbH-Y)71Vbo/0	involves: BALB/c * C57BL/6J * DBA/2J	MGI:3698744

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

hematopoietic system

decreased T cell proliferation ( J:86607 , J:154166 )

• 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)

abnormal thymus cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

• however, total thymic cellularity is only mildly decreased

abnormal thymocyte activation ( J:154166 )

• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells

abnormal T cell differentiation ( J:86607 )

• TCR^high mature thymocytes are decreased in number and ratio compared to wild-type, while TCR^low immature cells increase in thymus

abnormal T cell selection ( J:86607 )

• thmocytes exhibit abnormal sensitivity to both positive and negative selection

abnormal T cell clonal deletion ( J:154166 )

• defective clonal deletion of Vbeta5 and Vbeta11 thymocytes from endogenous viral superantigens, Mtv-8 and Mtv-9

abnormal positive T cell selection ( J:86607 , J:154166 )

• mice show positive thymic selection of arthritogenic autoimmune T cells (J:86607)

• numbers of the HSA^lo TCRbeta^hi cells are substantially decreased in mutant mice as compared with thymocytes from wild-type mice (J:154166)

increased B cell number ( J:86607 )

• B cell numbers are relatively increased

decreased CD4-positive, alpha-beta T cell number ( J:86607 , J:154166 )

• 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)

decreased CD8-positive, alpha-beta T cell number ( J:86607 , 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)

increased memory T cell number ( J:154166 )

• increase percentages of memory CD4 + T cells

decreased regulatory T cell number ( J:154166 )

• a marked reduction in both thymic T reg cell frequency as well as absolute T reg cell numbers

increased activated T cell number ( J:154166 )

• the percentages of CD45RB^lo CD4+ T cells were increased

abnormal splenic cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

increased immunoglobulin level ( J:86607 )

• mice display severe hypergammaglobulinemia

cellular

decreased T cell proliferation ( J:86607 , J:154166 )

• 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

decreased T cell proliferation ( J:86607 , J:154166 )

• 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)

abnormal thymus cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

• however, total thymic cellularity is only mildly decreased

abnormal thymocyte activation ( J:154166 )

• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells

abnormal T cell differentiation ( J:86607 )

• TCR^high mature thymocytes are decreased in number and ratio compared to wild-type, while TCR^low immature cells increase in thymus

abnormal T cell selection ( J:86607 )

• thmocytes exhibit abnormal sensitivity to both positive and negative selection

abnormal T cell clonal deletion ( J:154166 )

• defective clonal deletion of Vbeta5 and Vbeta11 thymocytes from endogenous viral superantigens, Mtv-8 and Mtv-9

abnormal positive T cell selection ( J:86607 , J:154166 )

• mice show positive thymic selection of arthritogenic autoimmune T cells (J:86607)

• numbers of the HSA^lo TCRbeta^hi cells are substantially decreased in mutant mice as compared with thymocytes from wild-type mice (J:154166)

increased B cell number ( J:86607 )

• B cell numbers are relatively increased

decreased CD4-positive, alpha-beta T cell number ( J:86607 , J:154166 )

• 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)

decreased CD8-positive, alpha-beta T cell number ( J:86607 , 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)

increased memory T cell number ( J:154166 )

• increase percentages of memory CD4 + T cells

decreased regulatory T cell number ( J:154166 )

• a marked reduction in both thymic T reg cell frequency as well as absolute T reg cell numbers

increased activated T cell number ( J:154166 )

• the percentages of CD45RB^lo CD4+ T cells were increased

abnormal splenic cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

increased immunoglobulin level ( J:86607 )

• mice display severe hypergammaglobulinemia

abnormal lymph node cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

increased interleukin-17 secretion ( J:154166 )

• the percentages of IL-17 producing cells are 15- fold higher than in the wild-type controls

decreased interleukin-2 secretion ( J:154166 )

• IL-2 production after CD3 stimulation was greatly reduced in mutant mice

increased susceptibility to induced arthritis ( J:154166 )

• mice develop Rheumatoid Factor antibodies after zymosan challenge

increased autoantibody level ( J:86607 )

• mice develop high titres of rheumatoid factor, autoantibodies to type II collagen, heat shock protein-70 and high levels of circulating immune complexes

rheumatoid arthritis ( J:86607 )

• by ~2 months of age

chronic joint inflammation ( J:86607 )

• swollen joints showed severe synovitis with subsynovial neutrophil, lymphocyte, macrophage and plasma cell infiltration

lung inflammation ( J:86607 )

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

skeleton

joint swelling ( J:86607 )

• 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

increased susceptibility to induced arthritis ( J:154166 )

• mice develop Rheumatoid Factor antibodies after zymosan challenge

rheumatoid arthritis ( J:86607 )

• by ~2 months of age

chronic joint inflammation ( J:86607 )

• swollen joints showed severe synovitis with subsynovial neutrophil, lymphocyte, macrophage and plasma cell infiltration

osteoporosis ( J:86607 )

• by 8-12 months of age

fused joints ( J:86607 )

• at 8-12 months of age, fusion of subchondral bones (wrist and ankle joints) is observed radiographically

joint dislocation ( J:86607 )

• dislocation of wrist and ankle joints is observed radiographically at 8-12 months of age

respiratory system

lung inflammation ( J:86607 )

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

integument

mixed cellular infiltration to dermis ( J:86607 )

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

endocrine/exocrine glands

abnormal thymus cell ratio ( J:154166 )

• significant decrease in the absolute number of CD4 and CD8 single positive subsets

• however, total thymic cellularity is only mildly decreased

abnormal thymocyte activation ( J:154166 )

• an attenuated TCR-induced increase in cytoplasmic free calcium in thymocytes and peripheral T cells

homeostasis/metabolism

joint swelling ( J:86607 )

• 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

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

Allelic Composition	Zap70^m1Saka/Zap70⁺
Genetic Background	involves: BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

normal phenotype

no abnormal phenotype detected ( J:86607 )

• mice do not develop arthritis or display immunological abnormalities seen in homozygotes

Allelic Composition	Zap70^m1Saka/Zap70^tm1Dlo
Genetic Background	involves: 129P2/OlaHsd * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)
Zap70^tm1Dlo mutation (0 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

immune system

autoimmune arthritis ( J:86607 )

• mice develop arthritis spontaneously by 3 months of age

skeleton

autoimmune arthritis ( J:86607 )

• mice develop arthritis spontaneously by 3 months of age

Allelic Composition	Zap70^m1Saka/Zap70^tm2.1Weis
Genetic Background	involves: 129S4/SvJae * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)
Zap70^tm2.1Weis mutation (1 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

hematopoietic system

abnormal T cell clonal deletion ( J:154166 )

• defects in the effectiveness of Mtv-8 and Mtv-9 induced clonal deletion in thymocyte cells bearing Vbeta5 and Vbeta11

immune system

abnormal T cell clonal deletion ( J:154166 )

• defects in the effectiveness of Mtv-8 and Mtv-9 induced clonal deletion in thymocyte cells bearing Vbeta5 and Vbeta11

decreased susceptibility to induced arthritis ( J:154166 )

• only 1 of 6 heterozygous mice develop mild arthritis during the 12-wk observation compared to the Zap70^m1Saka homozygous mice which all have severe arthritis

skeleton

decreased susceptibility to induced arthritis ( J:154166 )

• only 1 of 6 heterozygous mice develop mild arthritis during the 12-wk observation compared to the Zap70^m1Saka homozygous mice which all have severe arthritis

Allelic Composition	Zap70^m1Saka/Zap70^tm1Dlo Tg(Lck-ZAP70)824Saka/0
Genetic Background	involves: 129P2/OlaHsd * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Lck-ZAP70)824Saka mutation (0 available)
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)
Zap70^tm1Dlo mutation (0 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

normal phenotype

no abnormal phenotype detected ( J:86607 )

• expression of transgene completely inhibits development of arthritis and corrects immunological abnormalities observed in Zap70-deficient mice

Allelic Composition	Zap70^m1Saka/Zap70^m1Saka Tg(DO11.10)10Dlo/0
Genetic Background	involves: BALB/c * C3H * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(DO11.10)10Dlo mutation (7 available)
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

immune system

decreased T cell proliferation ( J:86607 )

• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells

decreased T cell number ( J:86607 )

• number of CD4+CD8- mature thymocytes decreases to ~20% that in control Tg(DO11.10)10Dlo mice

hematopoietic system

decreased T cell proliferation ( J:86607 )

• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells

decreased T cell number ( J:86607 )

• number of CD4+CD8- mature thymocytes decreases to ~20% that in control Tg(DO11.10)10Dlo mice

cellular

decreased T cell proliferation ( J:86607 )

• T cells require a 10-fold greater concentration of ovalbumin peptide to proliferate to the same extent and wild-type Tg(DO11.10)10Dlo T cells

Allelic Composition	Zap70^m1Saka/Zap70^m1Saka Tg(TcraH-Y,TcrbH-Y)71Vbo/0
Genetic Background	involves: BALB/c * C57BL/6J * DBA/2J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(TcraH-Y,TcrbH-Y)71Vbo mutation (4 available)
Zap70^m1Saka mutation (1 available); any Zap70 mutation (55 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

hematopoietic system

abnormal positive T cell selection ( J:86607 )

• female mice show almost no positive selection for transgenic CD8+CD4- thymocytes and T cells

• male transgenic mice show efficient positive selection of transgenic CD8+CD4- thymocytes

immune system

abnormal positive T cell selection ( J:86607 )

• female mice show almost no positive selection for transgenic CD8+CD4- thymocytes and T cells

• male transgenic mice show efficient positive selection of transgenic CD8+CD4- thymocytes

autoimmune arthritis ( J:86607 )

• mice develop arthritis with high incidence

skeleton

autoimmune arthritis ( J:86607 )

• mice develop arthritis with high incidence

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