Phenotypes associated with this allele

• Allele Symbol: Vav3^tm1Swat
• Allele Name: targeted mutation 1, Wojciech Swat
• Allele ID: MGI:2683642
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Vav3^tm1Swat/Vav3^tm1Swat	B6.129S6-Vav3^tm1Swat	MGI:4438043
hm2	Vav3^tm1Swat/Vav3^tm1Swat	involves: 129S6/SvEvTac * C57BL/6	MGI:4429588
cx3	Vav2^tm1Kdf/Vav2^tm1Kdf Vav3^tm1Swat/Vav3^tm1Swat	B6.129S-Vav2^tm1Kdf Vav3^tm1Swat	MGI:4438045
cx4	Vav2^tm1Tnr/Vav2^tm1Tnr Vav3^tm1Swat/Vav3^tm1Swat	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:3843266
cx5	Vav2^tm1Tnr/Vav2^tm1Tnr Vav3^tm1Swat/Vav3^tm1Swat	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3843260
cx6	Vav1^tm1Tyb/Vav1^tm1Tyb Vav2^tm1Kdf/Vav2^tm1Kdf Vav3^tm1Swat/Vav3^tm1Swat	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac	MGI:4362058
cx7	Vav1^tm1Tyb/Vav1^tm1Tyb Vav2^tm1Kdf/Vav2^tm1Kdf Vav3^tm1Swat/Vav3^tm1Swat	involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:2683655
cx8	Vav2^tm1Kdf/Vav2^tm1Kdf Vav3^tm1Swat/Vav3^tm1Swat	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6	MGI:4429591
cx9	Vav1^tm1Tyb/Vav1^tm1Tyb Vav3^tm1Swat/Vav3^tm1Swat	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:4429589

Genotype
MGI:4438043

hm1

• Allelic Composition: Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: B6.129S6-Vav3^tm1Swat

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

vision/eye

vision/eye phenotype ( J:158008 )

N • mice exhibit normal intraocular pressure and iridocorneal angle

Genotype
MGI:4429588

hm2

• Allelic Composition: Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:86654 )

• mice appear healthy and fertile, have normal lymphocyte development and show no major abnormalities

Genotype
MGI:4438045

cx3

• Allelic Composition: Vav2^tm1Kdf/Vav2^tm1Kdf; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: B6.129S-Vav2^tm1Kdf Vav3^tm1Swat

Vav2^tm1Kdf/Vav2^tm1Kdf Vav3^tm1Swat/Vav3^tm1Swat mice develop buphthalmos

vision/eye

abnormal eye morphology ( J:158008 )

• some eyes are atrophic and phthisical unlike in wild-type mice

• at 6 months, 75% of mice exhibit enlarged eyes compared with wild-type mice

retina ganglion cell degeneration ( J:158008 )

• at 15 and 30 weeks

optic nerve cupping ( J:158008 )

• at 10, 15, and 30 weeks

abnormal iridocorneal angle ( J:158008 )

• as early as 18 days, some mice exhibit closed iridocorneal angles unlike wild-type mice

• at 7 weeks, 50% of mice exhibit closed iridocorneal angles unlike wild-type mice

• at 12 to 16 weeks, 80% of mice exhibit closed iridocorneal angles unlike wild-type mice

anterior iris synechia ( J:158008 )

• between 18 days and 16 weeks, some mice exhibit peripheral anterior synechiae unlike wild-type mice

buphthalmos ( J:158008 )

• beginning at 6 to 12 weeks unilaterally then spreading bilaterally over the next 1 to 2 months with continued enlargement until 6 months of age

ocular hypertension ( J:158008 )

• 6 weeks, mice exhibit increased intraocular pressure compared with wild-type mice that increases further by 10 weeks of age

• mice with increased intraocular pressure exhibit closed iridocorneal angles

• however, treatment with ocular hypotensives such as latanoprost, dorzolamide and timolol produces a greater reduction in intraocular pressure than in similarly treated wild-type mice

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:158008 )

• treatment with Y27632 fails to lower intraocular pressure unlike in wild-type mice

increased physiological sensitivity to xenobiotic ( J:158008 )

• treatment with ocular hypotensives such as latanoprost, dorzolamide and timolol produces a greater reduction in intraocular pressure than in similarly treated wild-type mice

nervous system

retina ganglion cell degeneration ( J:158008 )

• at 15 and 30 weeks

optic nerve cupping ( J:158008 )

• at 10, 15, and 30 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glaucoma		DOID:1686		J:158008

Genotype
MGI:3843266

cx4

• Allelic Composition: Vav2^tm1Tnr/Vav2^tm1Tnr; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

cardiovascular system

decreased angiogenesis ( J:110334 )

• ephrin-A1-induced angiogenesis is impaired compared to in similarly exposed wild-type mice

abnormal vascular endothelial cell migration ( J:110334 )

• murine pulmonary microvascular endothelial cells (MPMECs) exhibit reduced ephrin-A1 migration compared with wild-type cells

• however, migration in response to serum is normal

abnormal vascular endothelial cell physiology ( J:110334 )

• on Matrigel, organization of murine pulmonary microvascular endothelial cells (MPMECs) into capillary-like structures is inhibited compared with similarly treated wild-type cells

cellular

abnormal vascular endothelial cell migration ( J:110334 )

• murine pulmonary microvascular endothelial cells (MPMECs) exhibit reduced ephrin-A1 migration compared with wild-type cells

• however, migration in response to serum is normal

abnormal cell adhesion ( J:110334 )

• mouse embryonic fibroblasts exhibit decreased spreading on an ephrin-A1-coated surface compared with wild-type cells

Genotype
MGI:3843260

cx5

• Allelic Composition: Vav2^tm1Tnr/Vav2^tm1Tnr; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

nervous system

abnormal axon guidance ( J:98310 )

• in culture, growth cones respond poorly to ephrin-A1 treatment compared to in wild-type cells

• however, growth cones respond normally to other repulsive guidance factors

abnormal sensory neuron innervation pattern ( J:98310 )

• ipsilateral projections from the retinal ganglion cells (RGCs) to the dorsal lateral geniculate nucleus are reduced in number and shifted ventrally compared to in wild-type

• RGC projections along the long axis are distorted compared to in wild-type mice

• ipsilateral RGC projections are shifted ventrolaterally and have a sloping distribution compared to in wild-type mice

cellular

abnormal axon guidance ( J:98310 )

• in culture, growth cones respond poorly to ephrin-A1 treatment compared to in wild-type cells

• however, growth cones respond normally to other repulsive guidance factors

Genotype
MGI:4362058

cx6

• Allelic Composition: Vav1^tm1Tyb/Vav1^tm1Tyb; Vav2^tm1Kdf/Vav2^tm1Kdf; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac

immune system

abnormal neutrophil physiology ( J:145345 )

• LPS- or peptidoglycan-stimulated reactive oxygen intermediate (ROI) production by neutrophils is blocked compared to in similarly treated wild-type cells

• however, ROI production in response to PMA stimulation is normal

abnormal NK cell physiology ( J:187430 )

• NK cells exhibit reduced conjugation with RMA-S cells compared with wild-type cells

abnormal macrophage physiology ( J:145345 )

• LPS-stimulated bone marrow-derived macrophages fail to generate oxidative burst unlike similarly treated wild-type cells

• however, mice exhibit normal bone marrow-derived macrophages response to PMA stimulation and reactive nitrogen and prostaglandin production in response to LPS

• despite normal phagocytosis, bone marrow-derived macrophages stimulated with unopsonized heat-killed E. coli fail to generate reactive oxygen intermediate unlike similarly treated wild-type cells

decreased interleukin-10 secretion ( J:145345 )

• from LPS-stimulated bone marrow-derived macrophages

decreased tumor necrosis factor secretion ( J:145345 )

• from LPS-stimulated bone marrow-derived macrophages

hematopoietic system

abnormal neutrophil physiology ( J:145345 )

• LPS- or peptidoglycan-stimulated reactive oxygen intermediate (ROI) production by neutrophils is blocked compared to in similarly treated wild-type cells

• however, ROI production in response to PMA stimulation is normal

abnormal NK cell physiology ( J:187430 )

• NK cells exhibit reduced conjugation with RMA-S cells compared with wild-type cells

abnormal macrophage physiology ( J:145345 )

• LPS-stimulated bone marrow-derived macrophages fail to generate oxidative burst unlike similarly treated wild-type cells

• however, mice exhibit normal bone marrow-derived macrophages response to PMA stimulation and reactive nitrogen and prostaglandin production in response to LPS

• despite normal phagocytosis, bone marrow-derived macrophages stimulated with unopsonized heat-killed E. coli fail to generate reactive oxygen intermediate unlike similarly treated wild-type cells

Genotype
MGI:2683655

cx7

• Allelic Composition: Vav1^tm1Tyb/Vav1^tm1Tyb; Vav2^tm1Kdf/Vav2^tm1Kdf; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S6/SvEvTac * C57BL/6

immune system

decreased B cell proliferation ( J:86654 )

• B cells fail to proliferate in response to Ig receptor stimulation

• mature B cells that are present in mutants fail to proliferate in response to stimulation with anti-Ig antibodies

decreased transitional stage T2 B cell number ( J:86654 )

• T2 cells are reduced approximately 2-fold

increased immature B cell number ( J:86654 )

• increase in the proportion of immature cells

increased transitional stage T1 B cell number ( J:86654 )

• numbers of transitional 1 (T1) and newly formed B cells are increased

arrested B cell differentiation ( J:86654 )

• immature B lineage cells accumulate in the periphery and development is arrested at a late transitional (T1/T2) stage

arrested T cell differentiation ( J:86654 )

• blocked at an early stage in the thymus, at the DN3 to DN4 transition

decreased mature B cell number ( J:86654 )

• 2- to 3-fold reduction in mature IgM^loIgD^hi B cells

decreased follicular B cell number ( J:86654 )

decreased marginal zone B cell number ( J:86654 )

decreased T cell number ( J:86654 )

• few peripheral T cells

decreased thymocyte number ( J:86654 )

• 50 to 100 fold reduction relative to wild-type

decreased double-positive T cell number ( J:86654 )

decreased single-positive T cell number ( J:86654 )

abnormal B cell calcium ion homeostasis ( J:86654 )

• anti-Ig induced calcium responses are severely disrupted in B cells

abnormal T cell physiology ( J:86654 )

• calcium fluxes induced by anti-CD3 antibody cross-linking are completely disrupted in T cells

decreased T cell proliferation ( J:86654 )

• T cells are unable to generate blasts when stimulated

• T cells do not exhibit proliferative responses to stimulation with anti-CD3 with or without anti-CD28 antibodies

abnormal humoral immune response ( J:86654 )

• failure to mount either T-dependent or T-independent humoral responses

decreased immunoglobulin level ( J:86654 )

• fail to produce any anti-TNP antibodies in response to TI-2 antigen

decreased IgG1 level ( J:86654 )

• fail to produce anti-TNP-specific IgG1 antibodies after immunization

decreased IgG2b level ( J:86654 )

• fail to produce anti-TNP-specific IgG2b antibodies after immunization

decreased IgG3 level ( J:86654 )

• fail to produce anti-TNP-specific IgG3 antibodies after immunization

decreased IgM level ( J:86654 )

• fail to produce anti-TNP-specific IgM antibodies after immunization

decreased interferon-gamma secretion ( J:86654 )

• mutant T cells do not produce IFN-gamma in response to TCR stimulation

decreased interleukin-2 secretion ( J:86654 )

• mutant T cells do not produce IL-2 in response to TCR stimulation

digestive/alimentary system

abnormal enterocyte morphology ( J:146174 )

• the upper zone surface of epithelial cells in the cecum and ascending colon are shorted than in wild-type mice

• epithelial cell heights in the cecum and ascending colon decrease between the middle and upper zones unlike in wild-type mice

• upper zone enterocyte differentiation, as determined by marker staining, is incomplete compared to in wild-type mice

intestinal ulcer ( J:146174 )

• beyond 6 weeks, mice develop spontaneous mucosal ulcers in the cecum and colon unlike wild-type mice

homeostasis/metabolism

abnormal B cell calcium ion homeostasis ( J:86654 )

• anti-Ig induced calcium responses are severely disrupted in B cells

impaired wound healing ( J:146174 )

• even after 10 days, mice fail to exhibit complete healing of colonic mucosa injury unlike similarly treated wild-type mice

hematopoietic system

decreased B cell proliferation ( J:86654 )

• B cells fail to proliferate in response to Ig receptor stimulation

• mature B cells that are present in mutants fail to proliferate in response to stimulation with anti-Ig antibodies

decreased transitional stage T2 B cell number ( J:86654 )

• T2 cells are reduced approximately 2-fold

increased immature B cell number ( J:86654 )

• increase in the proportion of immature cells

increased transitional stage T1 B cell number ( J:86654 )

• numbers of transitional 1 (T1) and newly formed B cells are increased

arrested B cell differentiation ( J:86654 )

• immature B lineage cells accumulate in the periphery and development is arrested at a late transitional (T1/T2) stage

arrested T cell differentiation ( J:86654 )

• blocked at an early stage in the thymus, at the DN3 to DN4 transition

decreased mature B cell number ( J:86654 )

• 2- to 3-fold reduction in mature IgM^loIgD^hi B cells

decreased follicular B cell number ( J:86654 )

decreased marginal zone B cell number ( J:86654 )

decreased T cell number ( J:86654 )

• few peripheral T cells

decreased thymocyte number ( J:86654 )

• 50 to 100 fold reduction relative to wild-type

decreased double-positive T cell number ( J:86654 )

decreased single-positive T cell number ( J:86654 )

abnormal B cell calcium ion homeostasis ( J:86654 )

• anti-Ig induced calcium responses are severely disrupted in B cells

decreased immunoglobulin level ( J:86654 )

• fail to produce any anti-TNP antibodies in response to TI-2 antigen

decreased IgG1 level ( J:86654 )

• fail to produce anti-TNP-specific IgG1 antibodies after immunization

decreased IgG2b level ( J:86654 )

• fail to produce anti-TNP-specific IgG2b antibodies after immunization

decreased IgG3 level ( J:86654 )

• fail to produce anti-TNP-specific IgG3 antibodies after immunization

decreased IgM level ( J:86654 )

• fail to produce anti-TNP-specific IgM antibodies after immunization

abnormal T cell physiology ( J:86654 )

• calcium fluxes induced by anti-CD3 antibody cross-linking are completely disrupted in T cells

decreased T cell proliferation ( J:86654 )

• T cells do not exhibit proliferative responses to stimulation with anti-CD3 with or without anti-CD28 antibodies

• T cells are unable to generate blasts when stimulated

endocrine/exocrine glands

decreased thymocyte number ( J:86654 )

• 50 to 100 fold reduction relative to wild-type

cellular

decreased B cell proliferation ( J:86654 )

• B cells fail to proliferate in response to Ig receptor stimulation

• mature B cells that are present in mutants fail to proliferate in response to stimulation with anti-Ig antibodies

decreased T cell proliferation ( J:86654 )

• T cells do not exhibit proliferative responses to stimulation with anti-CD3 with or without anti-CD28 antibodies

• T cells are unable to generate blasts when stimulated

Genotype
MGI:4429591

cx8

• Allelic Composition: Vav2^tm1Kdf/Vav2^tm1Kdf; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6

immune system

immune system phenotype ( J:86654 )

N • do not exhibit any obvious T cell abnormalities

Genotype
MGI:4429589

cx9

• Allelic Composition: Vav1^tm1Tyb/Vav1^tm1Tyb; Vav3^tm1Swat/Vav3^tm1Swat
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6

immune system

decreased B cell proliferation ( J:86654 )

• B cells show diminished proliferation in response to Ig receptor stimulation

decreased T cell proliferation ( J:86654 )

• T cells are unable to generate blasts when stimulated, indicating a proliferation defect

decreased mature B cell number ( J:86654 )

• small decrease in mature IgM^loIgD^hi B cells

decreased T cell number ( J:86654 )

• T cell numbers are reduced more than in single Vav1 homozygotes

• reduction in peripheral T cells

decreased double-negative T cell number ( J:86654 )

decreased double-positive T cell number ( J:86654 )

decreased single-positive T cell number ( J:86654 )

decreased interferon-gamma secretion ( J:86654 )

• mutant T cells do not produce IFN-gamma in response to TCR stimulation

decreased interleukin-2 secretion ( J:86654 )

• mutant T cells do not produce IL-2 in response to TCR stimulation

hematopoietic system

decreased B cell proliferation ( J:86654 )

• B cells show diminished proliferation in response to Ig receptor stimulation

decreased T cell proliferation ( J:86654 )

• T cells are unable to generate blasts when stimulated, indicating a proliferation defect

decreased mature B cell number ( J:86654 )

• small decrease in mature IgM^loIgD^hi B cells

decreased T cell number ( J:86654 )

• T cell numbers are reduced more than in single Vav1 homozygotes

• reduction in peripheral T cells

decreased double-negative T cell number ( J:86654 )

decreased double-positive T cell number ( J:86654 )

decreased single-positive T cell number ( J:86654 )

cellular

decreased B cell proliferation ( J:86654 )

• B cells show diminished proliferation in response to Ig receptor stimulation

decreased T cell proliferation ( J:86654 )

• T cells are unable to generate blasts when stimulated, indicating a proliferation defect