All Phenotypes Was<tm1Sbs> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Was^tm1Sbs/Was^tm1Sbs	129S6/SvEvTac-Was^tm1Sbs/J	MGI:5307127
hm2	Was^tm1Sbs/Was^tm1Sbs	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)	MGI:3525574
hm3	Was^tm1Sbs/Was^tm1Sbs	involves: 129S6/SvEvTac	MGI:3760283
hm4	Was^tm1Sbs/Was^tm1Sbs	involves: 129S6/SvEvTac * C57BL/6	MGI:5319488
hm5	Was^tm1Sbs/Was^tm1Sbs	involves: 129S/SvEv	MGI:3528193
hm6	Was^tm1Sbs/Was^tm1Sbs	involves: BALB/c	MGI:3528378
hm7	Was^tm1Sbs/Was^tm1Sbs	involves: C57BL/6 * CBA	MGI:3528064
cn8	Was^tm1Sbs/Was^tm1Sbs Wasl^tm2Sbs/Wasl^tm2Sbs Tg(Lck-cre)1Cwi/?	involves: 129S6/SvEvTac * C57BL/6	MGI:3760284
cx9	Cblb^tm1Pngr/Cblb^tm1Pngr Vav1^tm1Tyb/Vav1^tm1Tyb Was^tm1Sbs/Was^tm1Sbs	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac	MGI:3528380
cx10	Cblb^tm1Pngr/Cblb^tm1Pngr Was^tm1Sbs/Was^tm1Sbs	Not Specified	MGI:3528379
ot11	Was^tm1Sbs/Y	involves: 129S6/SvEvTac	MGI:4365300
ot12	Was^tm1Sbs/Y	involves: 129S6/SvEvTac * C57BL/6	MGI:5319489

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	129S6/SvEvTac-Was^tm1Sbs/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

homeostasis/metabolism

increased urine protein level ( J:180407 )

• mutants older than 6 months of age exhibit proteinuria

immune system

increased IgA level ( J:180407 )

• elevation in serum IgA, both in young and old mutants

• B cells exhibit increased IgA production after stimulation with LPS, TGF-beta1, IL-4, and IL-5

• reduced ratio of sialylated and galactosylated IgA in the serum, indicating that glycosylation of IgA is abnormal in mutants

• mutants exhibit higher titers of circulating IgA-containing complexes

• mutants exhibit increased glomerular IgA deposition in the kidneys

increased IgM level ( J:180407 )

• mutants exhibit increased glomerular IgM and C3 complement deposition in the kidneys

glomerulonephritis ( J:180407 )

• mutants develop proliferative glomerulonephritis similar to human IgA nephropathy

renal/urinary system

increased urine protein level ( J:180407 )

• mutants older than 6 months of age exhibit proteinuria

abnormal kidney morphology ( J:180407 )

• mutants exhibit renal injury with increasing severity with advancing age

glomerulonephritis ( J:180407 )

• mutants develop proliferative glomerulonephritis similar to human IgA nephropathy

abnormal glomerular mesangium morphology ( J:180407 )

• mutants older than 6 months of age exhibit hump-like mesangial and paramesangial deposits

increased mesangial cell number ( J:180407 )

• mutants older than 6 months of age, exhibit increased mesangial cellularity with or without endocapillary proliferation

expanded mesangial matrix ( J:180407 )

• mutants older than 6 months of age, exhibit increased matrix deposition with or without endocapillary proliferation

renal glomerular immunoglobulin deposits ( J:180407 )

• increased glomerular IgA deposition

hematopoietic system

increased IgA level ( J:180407 )

• elevation in serum IgA, both in young and old mutants

• B cells exhibit increased IgA production after stimulation with LPS, TGF-beta1, IL-4, and IL-5

• reduced ratio of sialylated and galactosylated IgA in the serum, indicating that glycosylation of IgA is abnormal in mutants

• mutants exhibit higher titers of circulating IgA-containing complexes

• mutants exhibit increased glomerular IgA deposition in the kidneys

increased IgM level ( J:180407 )

• mutants exhibit increased glomerular IgM and C3 complement deposition in the kidneys

cellular

increased mesangial cell number ( J:180407 )

• mutants older than 6 months of age, exhibit increased mesangial cellularity with or without endocapillary proliferation

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
IgA glomerulonephritis	DOID:2986	OMIM:161950	J:180407
Wiskott-Aldrich syndrome	DOID:9169	OMIM:301000	J:180407

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

neoplasm

neoplasm ( J:48836 )

N	• young mutant mice develop neither hematopoeitic malignancies nor eczema

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:48836 )

• severely affected colons appear dilated with thickened walls

• the intestinal mucosa appears thickened with crypt hyperplasia and a mixed lymphocytic and neutrophilic infiltrate within the lamina propria

crypts of Lieberkuhn abscesses ( J:48836 )

• mutants with severe colitis exhibit crypt abscesses

colitis ( J:48836 )

• most mutants develop chronic colitis by 4 months of age

• large numbers of CD4+ and CD8+ T cells (but not B220+ B cells) are scattered throughout the lamina propria in affected mutants

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:48836 )

• severely affected colons appear dilated with thickened walls

• the intestinal mucosa appears thickened with crypt hyperplasia and a mixed lymphocytic and neutrophilic infiltrate within the lamina propria

crypts of Lieberkuhn abscesses ( J:48836 )

• mutants with severe colitis exhibit crypt abscesses

hematopoietic system

decreased T cell proliferation ( J:48836 )

• in vitro, mutant T cells show defective proliferative responses and antigen receptor cap formation in reponse to anti-CD3epsilon mediated stimulation

increased neutrophil cell number ( J:48836 )

• in mutant mice, lymphopenia is associated with slightly increased numbers of neutrophils but normal numbers of red blood cells

thrombocytopenia ( J:48836 )

• mutants display modestly reduced numbers of platelets relative to wild-type mice

• notably, decreased platelet count is not associated with reduced platelet size or bleeding

decreased lymphocyte cell number ( J:48836 )

• mutants show a significant reduction in the number of peripheral blood lymphocytes, despite normal lymphocyte numbers in the spleen and lymph nodes

• young mutant mice (<10 weeks) exhibit comparable decreases in B and T cell numbers in peripheral blood, with no significant changes in blood B to T cell ratios

decreased B cell number ( J:48836 )

decreased T cell number ( J:48836 )

immune system

immune system phenotype ( J:48836 )

N	• mutants are viable, fertile and of normal weight, and exhibit normal lymphocyte development, serum immunoglobulin (Ig) levels and antibody responses relative to wild-type mice

decreased T cell proliferation ( J:48836 )

• in vitro, mutant T cells show defective proliferative responses and antigen receptor cap formation in reponse to anti-CD3epsilon mediated stimulation

colitis ( J:48836 )

• most mutants develop chronic colitis by 4 months of age

• large numbers of CD4+ and CD8+ T cells (but not B220+ B cells) are scattered throughout the lamina propria in affected mutants

increased neutrophil cell number ( J:48836 )

• in mutant mice, lymphopenia is associated with slightly increased numbers of neutrophils but normal numbers of red blood cells

decreased lymphocyte cell number ( J:48836 )

• mutants show a significant reduction in the number of peripheral blood lymphocytes, despite normal lymphocyte numbers in the spleen and lymph nodes

• young mutant mice (<10 weeks) exhibit comparable decreases in B and T cell numbers in peripheral blood, with no significant changes in blood B to T cell ratios

decreased B cell number ( J:48836 )

decreased T cell number ( J:48836 )

cellular

decreased T cell proliferation ( J:48836 )

• in vitro, mutant T cells show defective proliferative responses and antigen receptor cap formation in reponse to anti-CD3epsilon mediated stimulation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Wiskott-Aldrich syndrome		DOID:9169	OMIM:301000	J:48836

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

decreased T cell proliferation ( J:153247 )

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced compared to wild-type cells

• migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells

spleen hyperplasia ( J:153247 )

increased leukocyte cell number ( J:153247 )

increased monocyte cell number ( J:153247 )

abnormal dendritic cell morphology ( J:153247 )

• bone marrow-derived dendritic cell podosome turnover is increased compared to in wild-type mice

abnormal lymphocyte morphology ( J:153247 )

• the proportion of mature marginal zone to marginal zone precursors and T2 cells is decreased compared to in wild-type mice

abnormal double-negative T cell morphology ( J:125309 )

• the ratio of double negative 3 (DN3) to DN4 is skewed (1.49+/-0.90 compared to 0.74+/-0.45 in wild-type mice)

abnormal double-positive T cell morphology ( J:125309 )

• the percent of double positive (DP) CD69^high cells is greater than in wild-type

increased B cell number ( J:153247 )

• mice exhibit an increase in B220+ B cells in the spleen compared with wild-type mice

increased follicular B cell number ( J:153247 )

decreased NK cell number ( J:153247 )

• in the spleen

decreased T cell number ( J:153247 )

• mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

• fewer CD3+ T cells, especially CD8+CD3+ and CD4+CD8+Cd3+ T cells, are observed in the spleen, lymph nodes, and thymus than in wild-type mice

increased splenocyte number ( J:153247 )

abnormal dendritic cell physiology ( J:153247 )

• chemotaxis velocity bone marrow-derived dendritic cells in response to CCL3 is decreased compared to similarly treated wild-type cells

• migration of dendritic cells is impaired compared to wild-type cells

• dendritic cells fail to exhibit an increase in phagocytosis of latex beads unlike similarly treated wild-type cells

increased anti-double stranded DNA antibody level ( J:153247 )

• at a low titer

hematopoietic system

decreased T cell proliferation ( J:153247 )

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced compared to wild-type cells

• migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells

spleen hyperplasia ( J:153247 )

thrombocytopenia ( J:153247 )

increased leukocyte cell number ( J:153247 )

increased monocyte cell number ( J:153247 )

abnormal dendritic cell morphology ( J:153247 )

• bone marrow-derived dendritic cell podosome turnover is increased compared to in wild-type mice

abnormal lymphocyte morphology ( J:153247 )

• the proportion of mature marginal zone to marginal zone precursors and T2 cells is decreased compared to in wild-type mice

abnormal double-negative T cell morphology ( J:125309 )

• the ratio of double negative 3 (DN3) to DN4 is skewed (1.49+/-0.90 compared to 0.74+/-0.45 in wild-type mice)

abnormal double-positive T cell morphology ( J:125309 )

• the percent of double positive (DP) CD69^high cells is greater than in wild-type

increased B cell number ( J:153247 )

• mice exhibit an increase in B220+ B cells in the spleen compared with wild-type mice

increased follicular B cell number ( J:153247 )

decreased NK cell number ( J:153247 )

• in the spleen

decreased T cell number ( J:153247 )

• mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

• fewer CD3+ T cells, especially CD8+CD3+ and CD4+CD8+Cd3+ T cells, are observed in the spleen, lymph nodes, and thymus than in wild-type mice

increased splenocyte number ( J:153247 )

endocrine/exocrine glands

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced compared to wild-type cells

• migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells

cellular

decreased T cell proliferation ( J:153247 )

growth/size/body

spleen hyperplasia ( J:153247 )

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

increased germinal center B cell number ( J:182528 )

• in the spleen and lymph nodes

decreased mature B cell number ( J:182528 )

• decrease in the percentage and absolute number of bone marrow B220 hi mature recirculating B cells

decreased marginal zone B cell number ( J:182528 )

• decrease in the percentage and absolute number of marginal zone B cells

• the ring of B220+ CD1d+ MZ B cells that normally surrounds MOMA-expressing metallophilic macrophages is almost absent

increased plasma cell number ( J:182528 )

• increase in the proportion of CD19+ CD138^hi plasma cells

abnormal B cell physiology ( J:182528 )

• virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

• abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus

increased IgA level ( J:182528 )

increased IgE level ( J:182528 )

increased IgM level ( J:182528 )

• elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased autoantibody level ( J:182528 )

increased anti-chromatin antibody level ( J:182528 )

increased anti-double stranded DNA antibody level ( J:182528 )

increased anti-single stranded DNA antibody level ( J:182528 )

renal/urinary system

abnormal renal corpuscle morphology ( J:182528 )

• modest degree of glomerular damage

hematopoietic system

abnormal megakaryocyte morphology ( J:195436 )

• megakaryocytes fail to form podosomes when spread on collagen

• megakaryocytes exhibit reduced crossing protrussions compared with wild-type cells

• however, megakaryocytes spread normally on both collagen and fibrinogen

thrombocytopenia ( J:182528 )

increased germinal center B cell number ( J:182528 )

• in the spleen and lymph nodes

decreased mature B cell number ( J:182528 )

• decrease in the percentage and absolute number of bone marrow B220 hi mature recirculating B cells

decreased marginal zone B cell number ( J:182528 )

• decrease in the percentage and absolute number of marginal zone B cells

• the ring of B220+ CD1d+ MZ B cells that normally surrounds MOMA-expressing metallophilic macrophages is almost absent

increased plasma cell number ( J:182528 )

• increase in the proportion of CD19+ CD138^hi plasma cells

abnormal B cell physiology ( J:182528 )

• virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

• abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus

increased IgA level ( J:182528 )

increased IgE level ( J:182528 )

increased IgM level ( J:182528 )

• elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

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

cellular

abnormal osteoclast differentiation ( J:90542 )

• when cultured on glass coverslips, 67.9% of bone marrow osteoclasts from mutant mice are devoid of podosomes, assembling actin plaques that colocalize with vinculin

• on glass coverslips, 30.3% also assemble abnormal actin rings that are depleted of actin and vinculin and contain few podosome-like structures in the ring

• when cultured on bone slices, 52.7% of mutant osteoclasts are completely devoid of podosomes and fail to form actin rings at sealing zones; 45.8% display only abnormal actin-rich plaques that are undetectable in wild-type cells

• mutant osteoclasts exhibit a 7.9%- and a 1.8%-fold increase in the area of spreading on glass and bone, respectively, relative to wild-type

• increased area of spreading is associated with a 5.7%- and a 1.7%-fold increase in the number of nuclei per cell on glass and bone, respectively

• mutant osteoclasts are overall larger than wild-type but, in contrast to wild-type, do not undergo any further increase when plated on bone

abnormal cell migration ( J:84888 )

• in vitro, bone marrow cells from mutant mice show a 2-fold reduction in SDF-1-induced chemotaxis relative to wild-type cells

hematopoietic system

abnormal osteoclast differentiation ( J:90542 )

• when cultured on glass coverslips, 67.9% of bone marrow osteoclasts from mutant mice are devoid of podosomes, assembling actin plaques that colocalize with vinculin

• on glass coverslips, 30.3% also assemble abnormal actin rings that are depleted of actin and vinculin and contain few podosome-like structures in the ring

• mutant osteoclasts exhibit a 7.9%- and a 1.8%-fold increase in the area of spreading on glass and bone, respectively, relative to wild-type

• increased area of spreading is associated with a 5.7%- and a 1.7%-fold increase in the number of nuclei per cell on glass and bone, respectively

• mutant osteoclasts are overall larger than wild-type but, in contrast to wild-type, do not undergo any further increase when plated on bone

abnormal bone marrow cell morphology/development ( J:84888 )

• serial transplantation and competitive reconstitution expts show that marrow cells, including hematopoietic progenitors and stem cells (HSCs), from heterozgous carriers exhibit decreased migration and homing capacities relative to wild-type cells

• despite a normal marrow and spleen hematopoiesis, HSCs from mutant mice display a defect in their ability to colonize hematopoietic tissues associated with a defect in adhesion to collagen I

• HSCs expressing a normal gene appear to have a selective advantage over deficient cells in their capacity to migrate and home to the bone marrow

• authors propose that nonrandom X inactivation in heterozygous females is the consequence of a defect in the homing capacities of HSCs during fetal life

abnormal mast cell morphology ( J:86835 )

• mutant BMMC adhere to IgE-coated plates but are impaired in their ability to spread and form ruffles

abnormal mast cell physiology ( J:86835 )

• after 4 weeks of culture in IL3, bone marrow-derived mast cells (BMMC) from mutant mice show similar kinetics of cell growth and differentiation as wild-type BMMC

• notably, the numbers of tissue mast cells in ears of mutant mice are comparable to those of wild-type

• in vivo, mutant BMMC display diminished IgE-mediated mast cell degranulation with a significantly reduced rise in plasma histamine levels relative to wild-type

• in vitro, mutant BMMC display reduced IgE-mediated mast cell degranulation with a significant reduction in beta-hexosaminidase release relative to wild-type after IgE cross-linking

• in addition, mutant BMMC show reduced Ca2+ mobilization and deficient JNK activation after IgE cross-linking

abnormal osteoclast physiology ( J:90542 )

• following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

• despite low levels of bone loss, ovariectomized mutants show a 2.75-fold increase in total eroded surface, as well as a 1.5- and a 1.7-fold increase in the % of bone surface covered by osteoclasts and the total number of osteoclasts, respectively; no such increases are detected in wild-type

• consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro

immune system

abnormal osteoclast differentiation ( J:90542 )

• when cultured on glass coverslips, 67.9% of bone marrow osteoclasts from mutant mice are devoid of podosomes, assembling actin plaques that colocalize with vinculin

• on glass coverslips, 30.3% also assemble abnormal actin rings that are depleted of actin and vinculin and contain few podosome-like structures in the ring

• mutant osteoclasts exhibit a 7.9%- and a 1.8%-fold increase in the area of spreading on glass and bone, respectively, relative to wild-type

• increased area of spreading is associated with a 5.7%- and a 1.7%-fold increase in the number of nuclei per cell on glass and bone, respectively

• mutant osteoclasts are overall larger than wild-type but, in contrast to wild-type, do not undergo any further increase when plated on bone

abnormal mast cell morphology ( J:86835 )

• mutant BMMC adhere to IgE-coated plates but are impaired in their ability to spread and form ruffles

abnormal mast cell physiology ( J:86835 )

• after 4 weeks of culture in IL3, bone marrow-derived mast cells (BMMC) from mutant mice show similar kinetics of cell growth and differentiation as wild-type BMMC

• notably, the numbers of tissue mast cells in ears of mutant mice are comparable to those of wild-type

• in vivo, mutant BMMC display diminished IgE-mediated mast cell degranulation with a significantly reduced rise in plasma histamine levels relative to wild-type

• in vitro, mutant BMMC display reduced IgE-mediated mast cell degranulation with a significant reduction in beta-hexosaminidase release relative to wild-type after IgE cross-linking

• in addition, mutant BMMC show reduced Ca2+ mobilization and deficient JNK activation after IgE cross-linking

abnormal osteoclast physiology ( J:90542 )

• following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

• consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro

abnormal cytokine secretion ( J:86835 )

• mutant BMMC secrete significantly less IL6 and TNF than wild-type BMMC at 6, 24 and 48 h after IgE cross-linking

skeleton

abnormal osteoclast differentiation ( J:90542 )

• when cultured on glass coverslips, 67.9% of bone marrow osteoclasts from mutant mice are devoid of podosomes, assembling actin plaques that colocalize with vinculin

• on glass coverslips, 30.3% also assemble abnormal actin rings that are depleted of actin and vinculin and contain few podosome-like structures in the ring

• mutant osteoclasts exhibit a 7.9%- and a 1.8%-fold increase in the area of spreading on glass and bone, respectively, relative to wild-type

• increased area of spreading is associated with a 5.7%- and a 1.7%-fold increase in the number of nuclei per cell on glass and bone, respectively

• mutant osteoclasts are overall larger than wild-type but, in contrast to wild-type, do not undergo any further increase when plated on bone

abnormal osteoclast physiology ( J:90542 )

• following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

• consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	involves: BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

immune system phenotype ( J:84131 )

• in vitro, activated mutant B cells and DCs process and present soluble ovalbumin (whole OVA) or OVA 323-339 petides efficiently, with normal proliferative and cytokine responses in TCR tg CD4+ T cells

• notably, LPS-activated B cells, lacking microvilli, and (LPS+IL-4)-activated B cells, possessing many and long microvilli, exhibit a similar antigen processing and presenting capacity

• in vivo, immunization of mutant mice with OVA elicits proliferation of transferred, fluorescent-labelled, CD4+ T cells, confirming normal processing of soluble antigen and presentation on MHC class II molecules by APCs

decreased T cell proliferation ( J:84131 )

• mutant DCs present bacterial-derived OVA peptides but the T cell response is less than 50% of wild-type DCs, suggesting impaired processing of particulate antigen in DCs

abnormal dendritic cell antigen presentation ( J:84131 )

• DCs from mutant mice show impaired processing and presentation of particulate antigen (bacterial-expressed OVA)

hematopoietic system

decreased T cell proliferation ( J:84131 )

• mutant DCs present bacterial-derived OVA peptides but the T cell response is less than 50% of wild-type DCs, suggesting impaired processing of particulate antigen in DCs

cellular

decreased T cell proliferation ( J:84131 )

• mutant DCs present bacterial-derived OVA peptides but the T cell response is less than 50% of wild-type DCs, suggesting impaired processing of particulate antigen in DCs

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs
Genetic Background	involves: C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

abnormal B cell physiology ( J:95909 )

• mutant B cells display notable defects in polarization, spreading, and microvilli formation in response to IL-4- and CD40-dependent stimuli relative to similarly-induced wild-type B cells; homotypic aggregation is only mildly impaired

• activated mutant B lymphocytes exhibit an abnormally smooth surface and express shorter microvilli that are less dense in cell contacts than in activated wild-type B cells

hematopoietic system

abnormal B cell physiology ( J:95909 )

• activated mutant B lymphocytes exhibit an abnormally smooth surface and express shorter microvilli that are less dense in cell contacts than in activated wild-type B cells

Allelic Composition	Was^tm1Sbs/Was^tm1Sbs Wasl^tm2Sbs/Wasl^tm2Sbs Tg(Lck-cre)1Cwi/?
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Lck-cre)1Cwi mutation (3 available)
Wasl^tm2Sbs mutation (0 available); any Wasl mutation (39 available)
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

colitis ( J:125309 )

• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced

• migratory responses to CCL19 or CXCL12 are reduced even more than in Was^tm1Sbs homozygotes and compared to in wild-type cells

abnormal double-negative T cell morphology ( J:125309 )

• mice exhibit a reduction in large and cycling double negative 3 (DN3) cells and, to a lesser degree, DN4 cells

• the ratio of DN3 to DN4 is skewed (3.18+/-1.89 compared to 0.74+/-0.45 in wild-type mice and 1.49+/-0.90 in Was^tm1Sbs homozygotes)

abnormal double-positive T cell morphology ( J:125309 )

• the percent of double positive (DP) CD69^hi cells is greater than in wild-type

decreased T cell number ( J:125309 )

• the numbers of CD4+ and CD8+ T lymphocytes is reduced

decreased thymocyte number ( J:125309 )

• the number of thymocytes is reduced

• however, there is no increase in apoptosis

decreased regulatory T cell number ( J:125309 )

decreased single-positive T cell number ( J:125309 )

• mice have fewer single positive CD69^hi cells compared to in wild-type mice and Was^tm1Sbs homozygotes

increased single-positive T cell number ( J:125309 )

• the number of single positive CD69^low CD62L^low cells is increased compared to in wild-type mice

hematopoietic system

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced

• migratory responses to CCL19 or CXCL12 are reduced even more than in Was^tm1Sbs homozygotes and compared to in wild-type cells

abnormal double-negative T cell morphology ( J:125309 )

• mice exhibit a reduction in large and cycling double negative 3 (DN3) cells and, to a lesser degree, DN4 cells

• the ratio of DN3 to DN4 is skewed (3.18+/-1.89 compared to 0.74+/-0.45 in wild-type mice and 1.49+/-0.90 in Was^tm1Sbs homozygotes)

abnormal double-positive T cell morphology ( J:125309 )

• the percent of double positive (DP) CD69^hi cells is greater than in wild-type

decreased T cell number ( J:125309 )

• the numbers of CD4+ and CD8+ T lymphocytes is reduced

decreased thymocyte number ( J:125309 )

• the number of thymocytes is reduced

• however, there is no increase in apoptosis

decreased regulatory T cell number ( J:125309 )

decreased single-positive T cell number ( J:125309 )

• mice have fewer single positive CD69^hi cells compared to in wild-type mice and Was^tm1Sbs homozygotes

increased single-positive T cell number ( J:125309 )

• the number of single positive CD69^low CD62L^low cells is increased compared to in wild-type mice

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:125309 )

• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening

colitis ( J:125309 )

• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:125309 )

• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening

decreased thymocyte number ( J:125309 )

• the number of thymocytes is reduced

• however, there is no increase in apoptosis

abnormal thymocyte activation ( J:125309 )

• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

• spreading of TCR^high CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced

• migratory responses to CCL19 or CXCL12 are reduced even more than in Was^tm1Sbs homozygotes and compared to in wild-type cells

Allelic Composition	Cblb^tm1Pngr/Cblb^tm1Pngr Vav1^tm1Tyb/Vav1^tm1Tyb Was^tm1Sbs/Was^tm1Sbs
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cblb^tm1Pngr mutation (6 available); any Cblb mutation (58 available)
Vav1^tm1Tyb mutation (2 available); any Vav1 mutation (60 available)
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

abnormal T cell physiology ( J:79550 )

• introduction of the Cblb^tm1Pngr mutation into a Was^tm1Sbs/Vav1^tm1Tyb double null background fails to restore T cell responses and receptor clustering, indicating that WAS protein is critical for deregulated proliferation and membrane receptor reorganization of Cblb^tm1Pngr mutant T cells

hematopoietic system

abnormal T cell physiology ( J:79550 )

Allelic Composition	Cblb^tm1Pngr/Cblb^tm1Pngr Was^tm1Sbs/Was^tm1Sbs
Genetic Background	Not Specified

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cblb^tm1Pngr mutation (6 available); any Cblb mutation (58 available)
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

abnormal T cell physiology ( J:79550 )

• introduction of the Cblb^tm1Pngr mutation into a Was^tm1Sbs null background fails to restore T cell responses and receptor clustering, indicating that WAS protein is critical for deregulated proliferation and membrane receptor reorganization of Cblb^tm1Pngr mutant T cells

hematopoietic system

abnormal T cell physiology ( J:79550 )

Allelic Composition	Was^tm1Sbs/Y
Genetic Background	involves: 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

decreased T cell proliferation ( J:153247 )

spleen hyperplasia ( J:153247 )

increased leukocyte cell number ( J:153247 )

increased monocyte cell number ( J:153247 )

abnormal dendritic cell morphology ( J:153247 )

• bone marrow-derived dendritic cell podosome turnover is increased compared to in wild-type mice

abnormal lymphocyte morphology ( J:153247 )

• the proportion of mature marginal zone to marginal zone precursors and T2 cells is decreased compared to in wild-type mice

increased B cell number ( J:153247 )

• mice exhibit an increase in B220+ B cells in the spleen compared with wild-type mice

increased follicular B cell number ( J:153247 )

decreased NK cell number ( J:153247 )

• in the spleen

decreased T cell number ( J:153247 )

• mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

• fewer CD3+ T cells, especially CD8+CD3+ and CD4+CD8+Cd3+ T cells, are observed in the spleen, lymph nodes, and thymus than in wild-type mice

increased splenocyte number ( J:153247 )

abnormal dendritic cell physiology ( J:153247 )

• chemotaxis velocity bone marrow-derived dendritic cells in response to CCL3 is decreased compared to similarly treated wild-type cells

• migration of dendritic cells is impaired compared to wild-type cells

• dendritic cells fail to exhibit an increase in phagocytosis of latex beads unlike similarly treated wild-type cells

increased anti-double stranded DNA antibody level ( J:153247 )

• at a low titer

hematopoietic system

decreased T cell proliferation ( J:153247 )

spleen hyperplasia ( J:153247 )

thrombocytopenia ( J:153247 )

increased leukocyte cell number ( J:153247 )

increased monocyte cell number ( J:153247 )

abnormal dendritic cell morphology ( J:153247 )

• bone marrow-derived dendritic cell podosome turnover is increased compared to in wild-type mice

abnormal lymphocyte morphology ( J:153247 )

• the proportion of mature marginal zone to marginal zone precursors and T2 cells is decreased compared to in wild-type mice

increased B cell number ( J:153247 )

• mice exhibit an increase in B220+ B cells in the spleen compared with wild-type mice

increased follicular B cell number ( J:153247 )

decreased NK cell number ( J:153247 )

• in the spleen

decreased T cell number ( J:153247 )

• mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

• fewer CD3+ T cells, especially CD8+CD3+ and CD4+CD8+Cd3+ T cells, are observed in the spleen, lymph nodes, and thymus than in wild-type mice

increased splenocyte number ( J:153247 )

growth/size/body

spleen hyperplasia ( J:153247 )

cellular

decreased T cell proliferation ( J:153247 )

Allelic Composition	Was^tm1Sbs/Y
Genetic Background	involves: 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Was^tm1Sbs mutation (2 available); any Was mutation (12 available)

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

immune system

increased germinal center B cell number ( J:182528 )

• in the spleen and lymph nodes

decreased mature B cell number ( J:182528 )

• decrease in the percentage and absolute number of bone marrow B220 hi mature recirculating B cells

decreased marginal zone B cell number ( J:182528 )

• decrease in the percentage and absolute number of marginal zone B cells

• the ring of B220+ CD1d+ MZ B cells that normally surrounds MOMA-expressing metallophilic macrophages is almost absent

increased plasma cell number ( J:182528 )

• increase in the proportion of CD19+ CD138^hi plasma cells

abnormal B cell physiology ( J:182528 )

• virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

• abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus

increased IgA level ( J:182528 )

increased IgE level ( J:182528 )

increased IgM level ( J:182528 )

• elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased autoantibody level ( J:182528 )

increased anti-chromatin antibody level ( J:182528 )

increased anti-double stranded DNA antibody level ( J:182528 )

increased anti-single stranded DNA antibody level ( J:182528 )

renal/urinary system

abnormal renal corpuscle morphology ( J:182528 )

• modest degree of glomerular damage

hematopoietic system

thrombocytopenia ( J:182528 )

increased germinal center B cell number ( J:182528 )

• in the spleen and lymph nodes

decreased mature B cell number ( J:182528 )

• decrease in the percentage and absolute number of bone marrow B220 hi mature recirculating B cells

decreased marginal zone B cell number ( J:182528 )

• decrease in the percentage and absolute number of marginal zone B cells

• the ring of B220+ CD1d+ MZ B cells that normally surrounds MOMA-expressing metallophilic macrophages is almost absent

increased plasma cell number ( J:182528 )

• increase in the proportion of CD19+ CD138^hi plasma cells

abnormal B cell physiology ( J:182528 )

• virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

• abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus

increased IgA level ( J:182528 )

increased IgE level ( J:182528 )

increased IgM level ( J:182528 )

• elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

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