Overview

Also Known As:WASP-

These Was knock-out mice exhibit reduced peripheral blood lymphocyte counts and platelet numbers along with development of chronic colitis. They are suitable for use in applications related to the study of Wiskott-Aldrich syndrome in humans.

Donating Investigator

Dr. Frederick W. Alt, Children's Hospital

Genetic overview

Genetic Background	Generation

Was^tm1Sbs

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Was	Wiskott-Aldrich syndrome

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Mouse/Human Gene Homologs
Hematological Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

WAS-deficient mice are viable and fertile. Mutant mice show normal lymphocyte development, serum immunoglobulin (Ig) levels and antibody responses. However, peripheral blood lymphocyte counts and platelet numbers are reduced in these mice. Development of chronic colitis is also observed. In vitro, WAS-deficient T cells show markedly impaired proliferative responses to anti-CD3e mediated stimulation. The Was gene is X-linked, so hemizygous males are WAS deficient.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Snapper SB; Rosen FS; Mizoguchi E; Cohen P; Khan W; Liu CH; Hagemann TL; Kwan SP; Ferrini R; Davidson L; Bhan AK; Alt FW. 1998. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9(1):81-91PubMed: 9697838 MGI: J:48836

View All References

Genetics

Was^tm1Sbs

Allele Symbol: Was^tm1Sbs

Allele Name	targeted mutation 1, Scott B Snapper
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Was^-; wasp-
Gene Symbol and Name	Was, Wiskott-Aldrich syndrome
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	X
Molecular Note	A neomycin cassette was inserted into exon 7, which encodes part of the GTPase-binding domain. The absence of transcript and protein produced from the targeted allele in male hemizygous mutant mice was confirmed by Northern blot and Western blot analyses.
Mutations Made By	Dr. Scott Snapper, Massachusetts General Hospital

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Wiskott-Aldrich syndrome

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

IgA glomerulonephritis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Was^tm1Sbs related

Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
- Inflammation
  - Inflammatory bowel disease
- Immunodeficiency
- Intracellular Signaling Molecules
- T Cell Receptor Signaling Defects
Internal/Organ Research
- Gastrointestinal Defects
  - colitis
- Lymphoid Tissue Defects
Mouse/Human Gene Homologs
- Wiskott-Aldrich syndrome
Hematological Research
- Immunological Defects
- Platelet Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: C57BL/6 * CBA

hematopoietic system phenotype

abnormal B cell physiology
- 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
- 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

immune system phenotype

abnormal B cell physiology
- 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
- 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

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: BALB/c

cellular phenotype

decreased T cell proliferation
- 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

hematopoietic system phenotype

decreased T cell proliferation
- 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

immune system phenotype

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

decreased T cell proliferation
- 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

mammalian phenotype

immune system phenotype
- Normal - 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
- Normal - 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
- Normal - 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

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

abnormal B cell physiology
- abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus
- virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

abnormal megakaryocyte morphology
- Normal - however, megakaryocytes spread normally on both collagen and fibrinogen
- megakaryocytes exhibit reduced crossing protrussions compared with wild-type cells
- megakaryocytes fail to form podosomes when spread on collagen

decreased marginal zone B cell number
- 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

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

increased germinal center B cell number
- in the spleen and lymph nodes

increased IgA level

increased IgE level

increased IgM level
- elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased plasma cell number
- increase in the proportion of CD19+ CD138^hi plasma cells

thrombocytopenia

immune system phenotype

abnormal B cell physiology
- abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus
- virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

decreased marginal zone B cell number
- 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

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

increased anti-chromatin antibody level

increased anti-double stranded DNA antibody level

increased anti-single stranded DNA antibody level

increased autoantibody level

increased germinal center B cell number
- in the spleen and lymph nodes

increased IgA level

increased IgE level

increased IgM level
- elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased plasma cell number
- increase in the proportion of CD19+ CD138^hi plasma cells

renal/urinary system phenotype

abnormal renal corpuscle morphology
- modest degree of glomerular damage

Genotype: Was^tm1Sbs/Y
involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

abnormal B cell physiology
- abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus
- virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

decreased marginal zone B cell number
- 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

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

increased germinal center B cell number
- in the spleen and lymph nodes

increased IgA level

increased IgE level

increased IgM level
- elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased plasma cell number
- increase in the proportion of CD19+ CD138^hi plasma cells

thrombocytopenia

immune system phenotype

abnormal B cell physiology
- abrogation of the early response to immunization with UV inactivated vesicular stomatitis virus
- virtual abrogation of IgM and IgG pneumococcus polysaccharide specific Ab responses

decreased marginal zone B cell number
- 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

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

increased anti-chromatin antibody level

increased anti-double stranded DNA antibody level

increased anti-single stranded DNA antibody level

increased autoantibody level

increased germinal center B cell number
- in the spleen and lymph nodes

increased IgA level

increased IgE level

increased IgM level
- elevated total serum levels and spontaneous production of IgM Abs specific for trinitrophenyl and phosphocholine

increased plasma cell number
- increase in the proportion of CD19+ CD138^hi plasma cells

renal/urinary system phenotype

abnormal renal corpuscle morphology
- modest degree of glomerular damage

The following phenotype relates to a compound genotype created using this strain

Genotype: Was^tm1Sbs/Was^tm1Sbs
either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)

cellular phenotype

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

hematopoietic system phenotype

decreased B cell number

decreased lymphocyte cell number
- 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 T cell number

decreased T cell proliferation
- 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
- in mutant mice, lymphopenia is associated with slightly increased numbers of neutrophils but normal numbers of red blood cells

thrombocytopenia
- 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

immune system phenotype

colitis
- large numbers of CD4+ and CD8+ T cells (but not B220+ B cells) are scattered throughout the lamina propria in affected mutants
- most mutants develop chronic colitis by 4 months of age

decreased B cell number

decreased lymphocyte cell number
- 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 T cell number

decreased T cell proliferation
- 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
- in mutant mice, lymphopenia is associated with slightly increased numbers of neutrophils but normal numbers of red blood cells

digestive/alimentary phenotype

abnormal crypts of Lieberkuhn morphology
- 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

colitis
- large numbers of CD4+ and CD8+ T cells (but not B220+ B cells) are scattered throughout the lamina propria in affected mutants
- most mutants develop chronic colitis by 4 months of age

crypts of Lieberkuhn abscesses
- mutants with severe colitis exhibit crypt abscesses

mammalian phenotype

immune system phenotype
- Normal - 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

neoplasm
- Normal - young mutant mice develop neither hematopoeitic malignancies nor eczema

endocrine/exocrine gland phenotype

abnormal crypts of Lieberkuhn morphology
- 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
- mutants with severe colitis exhibit crypt abscesses

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S/SvEv

cellular phenotype

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

abnormal osteoclast differentiation
- 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
- 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
- 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
- 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

immune system phenotype

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

abnormal mast cell morphology
- mutant BMMC adhere to IgE-coated plates but are impaired in their ability to spread and form ruffles

abnormal mast cell physiology
- 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
- in addition, mutant BMMC show reduced Ca2+ mobilization and deficient JNK activation after IgE cross-linking
- 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 vivo, mutant BMMC display diminished IgE-mediated mast cell degranulation with a significantly reduced rise in plasma histamine levels relative to wild-type
- notably, the numbers of tissue mast cells in ears of mutant mice are comparable to those of wild-type

abnormal osteoclast differentiation
- 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
- 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
- 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
- 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

abnormal osteoclast physiology
- increases are detected in wild-type
- consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro
- 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
- following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

skeleton phenotype

abnormal osteoclast differentiation
- 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
- 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
- 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
- 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

abnormal osteoclast physiology
- increases are detected in wild-type
- consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro
- 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
- following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

hematopoietic system phenotype

abnormal bone marrow cell morphology/development
- authors propose that nonrandom X inactivation in heterozygous females is the consequence of a defect in the homing capacities of HSCs during fetal life
- 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
- 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

abnormal mast cell morphology
- mutant BMMC adhere to IgE-coated plates but are impaired in their ability to spread and form ruffles

abnormal mast cell physiology
- 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
- in addition, mutant BMMC show reduced Ca2+ mobilization and deficient JNK activation after IgE cross-linking
- 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 vivo, mutant BMMC display diminished IgE-mediated mast cell degranulation with a significantly reduced rise in plasma histamine levels relative to wild-type
- notably, the numbers of tissue mast cells in ears of mutant mice are comparable to those of wild-type

abnormal osteoclast differentiation
- 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
- 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
- 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
- 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

abnormal osteoclast physiology
- increases are detected in wild-type
- consistent with impaired bone resorption, mutant osteoclasts tend to form small excavations on bone slices in vitro
- 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
- following ovariectomy, mutants exhibit a non-significant 16.4% of bone loss relative to wild-type (38.6%)

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S6/SvEvTac

cellular phenotype

decreased T cell proliferation

endocrine/exocrine gland phenotype

abnormal thymocyte activation
- migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells
- 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
- unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

immune system phenotype

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

abnormal dendritic cell physiology
- chemotaxis velocity bone marrow-derived dendritic cells in response to CCL3 is decreased compared to similarly treated wild-type cells
- dendritic cells fail to exhibit an increase in phagocytosis of latex beads unlike similarly treated wild-type cells
- migration of dendritic cells is impaired compared to wild-type cells

abnormal double-negative T cell morphology
- 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
- the percent of double positive (DP) CD69^high cells is greater than in wild-type

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

abnormal thymocyte activation
- migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells
- 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
- unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

decreased NK cell number
- in the spleen

decreased T cell number
- 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
- mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

decreased T cell proliferation

increased anti-double stranded DNA antibody level
- at a low titer

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

increased follicular B cell number

increased leukocyte cell number

increased monocyte cell number

increased splenocyte number

spleen hyperplasia

growth/size/body region phenotype

spleen hyperplasia

hematopoietic system phenotype

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

abnormal double-negative T cell morphology
- 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
- the percent of double positive (DP) CD69^high cells is greater than in wild-type

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

abnormal thymocyte activation
- migratory responses to CCL19 or CXCL12 are reduced compared to in wild-type cells
- 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
- unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation

decreased NK cell number
- in the spleen

decreased T cell number
- 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
- mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

decreased T cell proliferation

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

increased follicular B cell number

increased leukocyte cell number

increased monocyte cell number

increased splenocyte number

spleen hyperplasia

thrombocytopenia

Genotype: Was^tm1Sbs/Y
involves: 129S6/SvEvTac

cellular phenotype

decreased T cell proliferation

immune system phenotype

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

abnormal dendritic cell physiology
- chemotaxis velocity bone marrow-derived dendritic cells in response to CCL3 is decreased compared to similarly treated wild-type cells
- dendritic cells fail to exhibit an increase in phagocytosis of latex beads unlike similarly treated wild-type cells
- migration of dendritic cells is impaired compared to wild-type cells

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

decreased NK cell number
- in the spleen

decreased T cell number
- 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
- mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

decreased T cell proliferation

increased anti-double stranded DNA antibody level
- at a low titer

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

increased follicular B cell number

increased leukocyte cell number

increased monocyte cell number

increased splenocyte number

spleen hyperplasia

growth/size/body region phenotype

spleen hyperplasia

hematopoietic system phenotype

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

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

decreased NK cell number
- in the spleen

decreased T cell number
- 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
- mice have fewer CD4+ CD3+ and CD8+ CD3+ T cells than in wild-type mice

decreased T cell proliferation

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

increased follicular B cell number

increased leukocyte cell number

increased monocyte cell number

increased splenocyte number

spleen hyperplasia

thrombocytopenia

Genotype: Was^tm1Sbs/Was^tm1Sbs
129S6/SvEvTac-Was/J

hematopoietic system phenotype

increased IgA level
- B cells exhibit increased IgA production after stimulation with LPS, TGF-beta1, IL-4, and IL-5
- elevation in serum IgA, both in young and old mutants
- mutants exhibit higher titers of circulating IgA-containing complexes
- mutants exhibit increased glomerular IgA deposition in the kidneys
- reduced ratio of sialylated and galactosylated IgA in the serum, indicating that glycosylation of IgA is abnormal in mutants

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

renal/urinary system phenotype

abnormal glomerular mesangium morphology
- mutants older than 6 months of age exhibit hump-like mesangial and paramesangial deposits

abnormal kidney morphology
- mutants exhibit renal injury with increasing severity with advancing age

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

glomerulonephritis
- mutants develop proliferative glomerulonephritis similar to human IgA nephropathy

increased urine protein level
- mutants older than 6 months of age exhibit proteinuria

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

renal glomerular immunoglobulin deposits
- increased glomerular IgA deposition

homeostasis/metabolism phenotype

increased urine protein level
- mutants older than 6 months of age exhibit proteinuria

immune system phenotype

glomerulonephritis
- mutants develop proliferative glomerulonephritis similar to human IgA nephropathy

increased IgA level
- B cells exhibit increased IgA production after stimulation with LPS, TGF-beta1, IL-4, and IL-5
- elevation in serum IgA, both in young and old mutants
- mutants exhibit higher titers of circulating IgA-containing complexes
- mutants exhibit increased glomerular IgA deposition in the kidneys
- reduced ratio of sialylated and galactosylated IgA in the serum, indicating that glycosylation of IgA is abnormal in mutants

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

References

Snapper SB; Rosen FS; Mizoguchi E; Cohen P; Khan W; Liu CH; Hagemann TL; Kwan SP; Ferrini R; Davidson L; Bhan AK; Alt FW. 1998. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9(1):81-91PubMed: 9697838 MGI: J:48836

Additional References

Cannon JL; Burkhardt JK. 2004. Differential roles for Wiskott-Aldrich syndrome protein in immune synapse formation and IL-2 production. J Immunol 173(3):1658-62PubMed: 15265894 MGI: J:92036

Additional - Was^tm1Sbs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Was
- Separated PCR:Was
- Genotyping resources and troubleshooting
Citation
When using the WASP- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003292 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Homozygous Females and hemizygous males for Tac-Was<tm1Sbs>, 1 pair minimum

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:WASP-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Approximate Controls

Additional Information

Selected References

Wastm1Sbs

Allele Symbol: Wastm1Sbs

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Wastm1Sbs related

Mammalian Phenotype Terms by Genotype

Genotype: Wastm1Sbs/Wastm1Sbsinvolves: C57BL/6 * CBA

hematopoietic system phenotype

immune system phenotype

Genotype: Wastm1Sbs/Wastm1Sbsinvolves: BALB/c

cellular phenotype

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

Genotype: Wastm1Sbs/Wastm1Sbsinvolves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

immune system phenotype

renal/urinary system phenotype

Genotype: Wastm1Sbs/Yinvolves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

immune system phenotype

renal/urinary system phenotype

Genotype: Wastm1Sbs/Wastm1Sbseither: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)

cellular phenotype

hematopoietic system phenotype

immune system phenotype

digestive/alimentary phenotype

mammalian phenotype

endocrine/exocrine gland phenotype

Genotype: Wastm1Sbs/Wastm1Sbsinvolves: 129S/SvEv

cellular phenotype

immune system phenotype

skeleton phenotype

hematopoietic system phenotype

Genotype: Wastm1Sbs/Wastm1Sbsinvolves: 129S6/SvEvTac

cellular phenotype

endocrine/exocrine gland phenotype

immune system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Wastm1Sbs/Yinvolves: 129S6/SvEvTac

cellular phenotype

immune system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Wastm1Sbs/Wastm1Sbs129S6/SvEvTac-Was/J

hematopoietic system phenotype

renal/urinary system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - Wastm1Sbs related

Genotyping Protocols

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

Was^tm1Sbs

Allele Symbol: Was^tm1Sbs

Genotype: Was^tm1Sbs related

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: C57BL/6 * CBA

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: BALB/c

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S6/SvEvTac * C57BL/6

Genotype: Was^tm1Sbs/Y
involves: 129S6/SvEvTac * C57BL/6

Genotype: Was^tm1Sbs/Was^tm1Sbs
either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S/SvEv

Genotype: Was^tm1Sbs/Was^tm1Sbs
involves: 129S6/SvEvTac

Genotype: Was^tm1Sbs/Y
involves: 129S6/SvEvTac

Genotype: Was^tm1Sbs/Was^tm1Sbs
129S6/SvEvTac-Was/J

Additional - Was^tm1Sbs related