Phenotypes associated with this allele

• Allele Symbol: Rac2^tm1Mddw
• Allele Name: targeted mutation 1, Mary C Dinauer and David A Williams
• Allele ID: MGI:1857701
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rac2^tm1Mddw/Rac2^tm1Mddw	B6.129S-Rac2^tm1Mddw	MGI:4438259
hm2	Rac2^tm1Mddw/Rac2^tm1Mddw	involves: 129S/SvEv	MGI:3840468
hm3	Rac2^tm1Mddw/Rac2^tm1Mddw	involves: 129S/SvEv * C57BL/6	MGI:3840460
cn4	Cd19^tm1(cre)Cgn/Cd19^+ Rac1^tm1Tyb/Rac1^tm1Tyb Rac2^tm1Mddw/Rac2^tm1Mddw	involves: 129P2/OlaHsd * 129S/SvEv * 129S4/SvJae * C57BL/6	MGI:2684442
cx5	Rac2^tm1Mddw/Rac2^tm1Mddw Tg(TcrAND)53Hed/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:3840504

Genotype
MGI:4438259

hm1

• Allelic Composition: Rac2^tm1Mddw/Rac2^tm1Mddw
• Genetic Background: B6.129S-Rac2^tm1Mddw

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

immune system

abnormal neutrophil physiology ( J:83457 )

• mutant bone marrow neutrophils show a significant decrease in PMA-elicited NADPH oxidase activity relative to wild-type controls; however, the overall kinetics of PMA-induced superoxide production are normal

• mutant bone marrow neutrophils show a significant decrease in fMLP-elicited NADPH oxidase activity relative to wild-type controls; both a delay in reaching maximal enzyme activity and an overall decrease in superoxide production are observed

hematopoietic system

abnormal neutrophil physiology ( J:83457 )

• mutant bone marrow neutrophils show a significant decrease in PMA-elicited NADPH oxidase activity relative to wild-type controls; however, the overall kinetics of PMA-induced superoxide production are normal

• mutant bone marrow neutrophils show a significant decrease in fMLP-elicited NADPH oxidase activity relative to wild-type controls; both a delay in reaching maximal enzyme activity and an overall decrease in superoxide production are observed

Genotype
MGI:3840468

hm2

• Allelic Composition: Rac2^tm1Mddw/Rac2^tm1Mddw
• Genetic Background: involves: 129S/SvEv

homeostasis/metabolism

abnormal wound healing ( J:131305 )

• lipid peroxidation, respiratory burst activity of neutrophils, and proliferation of vascular endothelial cells, measured by CD31 staining, at the wound site is decreased compared to in wild-type mice

delayed wound healing ( J:131305 )

• delayed wound healing is associated with a 3-fold decrease in superoxide production at the wound site and a decrease in peroxide concentration in wound fluid compared to in similarly treated wild-type mice

cellular

decreased vascular endothelial cell proliferation ( J:131305 )

• proliferation of vascular endothelial cells at a wound site is decreased compared to in wild-type mice

cardiovascular system

decreased angiogenesis ( J:131305 )

• proliferation of vascular endothelial cells at a wound site is decreased compared to in wild-type mice

decreased vascular endothelial cell proliferation ( J:131305 )

• proliferation of vascular endothelial cells at a wound site is decreased compared to in wild-type mice

immune system

abnormal neutrophil physiology ( J:131305 )

• respiratory burst activity of neutrophils at a wound site is decreased compared to in wild-type mice

hematopoietic system

abnormal neutrophil physiology ( J:131305 )

• respiratory burst activity of neutrophils at a wound site is decreased compared to in wild-type mice

Genotype
MGI:3840460

hm3

• Allelic Composition: Rac2^tm1Mddw/Rac2^tm1Mddw
• Genetic Background: involves: 129S/SvEv * C57BL/6

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:53362 )

• Aspergillus fumigatus-infected mice exhibit increased mortality and decreased survival time compared to similarly treated wild-type mice

immune system

abnormal granulocyte differentiation ( J:53362 )

• mice exhibit a modest excess of mature granulopoiesis in the bone marrow compared to in wild-type mice

decreased T cell proliferation ( J:119437 )

• following anti-CD3 antibody stimulation, T cell proliferation is decreased compared to similarly treated wild-type cells

• CD4+ T cell proliferation in response to anti-CD3 antibodies is decreased 2-fold compared to similarly treated wild-type cells

• however, co-stimulation with anti-CD28 antibodies or the addition of IL2 can partially compensate for reduced proliferation of T cells

decreased leukocyte cell number ( J:53362 )

• at 4 post-thioglycollate treatment, peritoneal exudates exhibit reduced leukocyte numbers compared to in wild-type mice

decreased neutrophil cell number ( J:53362 )

• at 4 and 18 hours post-thioglycollate treatment, peritoneal exudates exhibit reduced neutrophils numbers compared to in wild-type mice

increased leukocyte cell number ( J:53362 )

• 1.9-fold higher than in wild-type mice

increased neutrophil cell number ( J:53362 )

• mice exhibit a 2.5- to 3-fold increased in neutrophil numbers compared to in wild-type mice

abnormal neutrophil physiology ( J:53362 )

• PMA and NADPH-stimulated bone marrow neutrophils exhibit 23% of normal superoxide production

• however, peritoneal exudate neutrophils exhibit normal superoxide production following thioglycollate stimulation

• TNF-alpha and PMA-stimulated bone marrow neutrophils exhibit a 61% of normal superoxide production

• neutrophil integrin adhesion is decreased compared to wild-type cells

• chemotaxis of bone marrow neutrophils is decreased 4- to 10-fold compared to wild-type cells

impaired neutrophil chemotaxis ( J:53362 )

• spreading of neutrophils over glass cover slips is 76% of that observed in wild-type cells

increased susceptibility to bacterial infection ( J:53362 )

• Aspergillus fumigatus-infected mice exhibit increased mortality and decreased survival time compared to similarly treated wild-type mice

• 4 to 6 days post-infection with A. fumigatus, recovery of viable A. fumigatus in the brain and kidney is increased 9.2 and 5.5 times compared to in similarly treated wild-type mice

• foci of hyphae in the renal parenchyma of A. fumigatus-infected mice are surrounded by an exuberant neutrophil infiltrate unlike in wild-type mice

hematopoietic system

abnormal granulocyte differentiation ( J:53362 )

• mice exhibit a modest excess of mature granulopoiesis in the bone marrow compared to in wild-type mice

decreased T cell proliferation ( J:119437 )

• following anti-CD3 antibody stimulation, T cell proliferation is decreased compared to similarly treated wild-type cells

• CD4+ T cell proliferation in response to anti-CD3 antibodies is decreased 2-fold compared to similarly treated wild-type cells

• however, co-stimulation with anti-CD28 antibodies or the addition of IL2 can partially compensate for reduced proliferation of T cells

decreased leukocyte cell number ( J:53362 )

• at 4 post-thioglycollate treatment, peritoneal exudates exhibit reduced leukocyte numbers compared to in wild-type mice

decreased neutrophil cell number ( J:53362 )

• at 4 and 18 hours post-thioglycollate treatment, peritoneal exudates exhibit reduced neutrophils numbers compared to in wild-type mice

increased leukocyte cell number ( J:53362 )

• 1.9-fold higher than in wild-type mice

increased neutrophil cell number ( J:53362 )

• mice exhibit a 2.5- to 3-fold increased in neutrophil numbers compared to in wild-type mice

abnormal neutrophil physiology ( J:53362 )

• PMA and NADPH-stimulated bone marrow neutrophils exhibit 23% of normal superoxide production

• however, peritoneal exudate neutrophils exhibit normal superoxide production following thioglycollate stimulation

• TNF-alpha and PMA-stimulated bone marrow neutrophils exhibit a 61% of normal superoxide production

• neutrophil integrin adhesion is decreased compared to wild-type cells

• chemotaxis of bone marrow neutrophils is decreased 4- to 10-fold compared to wild-type cells

impaired neutrophil chemotaxis ( J:53362 )

• spreading of neutrophils over glass cover slips is 76% of that observed in wild-type cells

cellular

abnormal granulocyte differentiation ( J:53362 )

• mice exhibit a modest excess of mature granulopoiesis in the bone marrow compared to in wild-type mice

impaired neutrophil chemotaxis ( J:53362 )

• spreading of neutrophils over glass cover slips is 76% of that observed in wild-type cells

decreased T cell proliferation ( J:119437 )

• following anti-CD3 antibody stimulation, T cell proliferation is decreased compared to similarly treated wild-type cells

• CD4+ T cell proliferation in response to anti-CD3 antibodies is decreased 2-fold compared to similarly treated wild-type cells

• however, co-stimulation with anti-CD28 antibodies or the addition of IL2 can partially compensate for reduced proliferation of T cells

Genotype
MGI:2684442

cn4

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Rac1^tm1Tyb/Rac1^tm1Tyb; Rac2^tm1Mddw/Rac2^tm1Mddw
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * 129S4/SvJae * C57BL/6

hematopoietic system

arrested B cell differentiation ( J:86765 )

• development blocked at the T1 stage

decreased B cell number ( J:86765 )

decreased transitional stage B cell number ( J:86765 )

• diminished splenic T1 and T2 cells

decreased B-1 B cell number ( J:86765 )

• peritoneal B cells (B1) also reduced

decreased follicular B cell number ( J:86765 )

• diminished recirculating follicular B cells

decreased marginal zone B cell number ( J:86765 )

• splenic marginal B cells were reduced

immune system

arrested B cell differentiation ( J:86765 )

• development blocked at the T1 stage

decreased B cell number ( J:86765 )

decreased transitional stage B cell number ( J:86765 )

• diminished splenic T1 and T2 cells

decreased B-1 B cell number ( J:86765 )

• peritoneal B cells (B1) also reduced

decreased follicular B cell number ( J:86765 )

• diminished recirculating follicular B cells

decreased marginal zone B cell number ( J:86765 )

• splenic marginal B cells were reduced

Genotype
MGI:3840504

cx5

• Allelic Composition: Rac2^tm1Mddw/Rac2^tm1Mddw; Tg(TcrAND)53Hed/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

immune system

abnormal T cell activation ( J:119437 )

• following TCR stimulation, calcium mobilization in CD4+ T cells is decreased compared to in similarly treated wild-type cells

decreased T cell proliferation ( J:119437 )

• T cell proliferation is 2- to 3-fold lower following stimulation with I-E^K+ or fibroblast APC expressing with I-E^K+ and B7 molecules compared to in similarly treated wild-type cells

decreased circulating interleukin-2 level ( J:119437 )

• following stimulation with TCR-specific antigen

homeostasis/metabolism

decreased circulating interleukin-2 level ( J:119437 )

• following stimulation with TCR-specific antigen

hematopoietic system

abnormal T cell activation ( J:119437 )

• following TCR stimulation, calcium mobilization in CD4+ T cells is decreased compared to in similarly treated wild-type cells

decreased T cell proliferation ( J:119437 )

• T cell proliferation is 2- to 3-fold lower following stimulation with I-E^K+ or fibroblast APC expressing with I-E^K+ and B7 molecules compared to in similarly treated wild-type cells

cellular

decreased T cell proliferation ( J:119437 )

• T cell proliferation is 2- to 3-fold lower following stimulation with I-E^K+ or fibroblast APC expressing with I-E^K+ and B7 molecules compared to in similarly treated wild-type cells