Phenotypes associated with this allele

• Allele Symbol: Wipf1^tm1Geha
• Allele Name: targeted mutation 1, Raif S Geha
• Allele ID: MGI:2178802
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wipf1^tm1Geha/Wipf1^tm1Geha	involves: 129S6/SvEvTac	MGI:2653663
hm2	Wipf1^tm1Geha/Wipf1^tm1Geha	involves: 129S6/SvEvTac * C57BL/6	MGI:5795857

Genotype
MGI:2653663

hm1

• Allelic Composition: Wipf1^tm1Geha/Wipf1^tm1Geha
• Genetic Background: involves: 129S6/SvEvTac

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

immune system

increased B cell proliferation ( J:74719 )

• B lymphocytes exhibit increased proliferation in response to stimulation

thymus hypoplasia ( J:74719 )

• reduced thymus cellularity in 6-10 week old mutants

decreased thymocyte number ( J:74719 )

increased IgE level ( J:74719 )

• in 6-8 week old mutants

increased IgM level ( J:74719 )

• in 6-8 week old mutants

abnormal T cell physiology ( J:74719 )

• T cells fail to secrete IL-2, to increase their F-actin content, to polarize, and to extend protrusions following T cell receptor ligation and are deficient in conjugate formation with superantigen-presenting B cells and anti-CD3 bilayers

decreased T cell proliferation ( J:74719 )

• impaired T cell activation: T cell proliferation in response to plate-bound anti-CD3 is abolished and T cells fail to secrete detectable IL-2 after CD3 ligation

hematopoietic system

increased B cell proliferation ( J:74719 )

• B lymphocytes exhibit increased proliferation in response to stimulation

thymus hypoplasia ( J:74719 )

• reduced thymus cellularity in 6-10 week old mutants

decreased thymocyte number ( J:74719 )

increased IgE level ( J:74719 )

• in 6-8 week old mutants

increased IgM level ( J:74719 )

• in 6-8 week old mutants

abnormal T cell physiology ( J:74719 )

• T cells fail to secrete IL-2, to increase their F-actin content, to polarize, and to extend protrusions following T cell receptor ligation and are deficient in conjugate formation with superantigen-presenting B cells and anti-CD3 bilayers

decreased T cell proliferation ( J:74719 )

• impaired T cell activation: T cell proliferation in response to plate-bound anti-CD3 is abolished and T cells fail to secrete detectable IL-2 after CD3 ligation

endocrine/exocrine glands

thymus hypoplasia ( J:74719 )

• reduced thymus cellularity in 6-10 week old mutants

decreased thymocyte number ( J:74719 )

cellular

increased B cell proliferation ( J:74719 )

• B lymphocytes exhibit increased proliferation in response to stimulation

decreased T cell proliferation ( J:74719 )

• impaired T cell activation: T cell proliferation in response to plate-bound anti-CD3 is abolished and T cells fail to secrete detectable IL-2 after CD3 ligation

Genotype
MGI:5795857

hm2

• Allelic Composition: Wipf1^tm1Geha/Wipf1^tm1Geha
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:116168 )

• mice die suddenly between 14 and 40 weeks of age

digestive/alimentary system

crypts of Lieberkuhn abscesses ( J:116168 )

• microabscesses in the crypts

abnormal gastric surface mucous cell morphology ( J:116168 )

• decrease in the number of mucus-secreting cells

abnormal stomach glandular epithelium morphology ( J:116168 )

• alterations and lesions of the glandular epithelium

colitis ( J:116168 )

• 3 of 7 and 4 of 5 mice show indications of ulcerative colitis at 8 weeks and 16 weeks of age, respectively

• all mice exhibit severe colitis aggravated by fibrosis and mucosal pseudopolyposis at 36 weeks of age

endocrine/exocrine glands

crypts of Lieberkuhn abscesses ( J:116168 )

• microabscesses in the crypts

abnormal thymus morphology ( J:116168 )

• cellularity of thymus is slightly reduced in 8 week old mutants

• however, no alterations in the cortex and medulla are seen

decreased thymus weight ( J:116168 )

• weight of thymus is slightly reduced in 8 week old mutants

hematopoietic system

abnormal thymus morphology ( J:116168 )

• cellularity of thymus is slightly reduced in 8 week old mutants

• however, no alterations in the cortex and medulla are seen

decreased thymus weight ( J:116168 )

• weight of thymus is slightly reduced in 8 week old mutants

abnormal hemopoiesis ( J:116168 )

• hemopoiesis is mainly directed to the production of granulocytes

abnormal erythropoiesis ( J:116168 )

• bone marrow erythropoiesis is deficient

abnormal lymphopoiesis ( J:116168 )

• bone marrow lymphopoiesis is deficient

abnormal bone marrow cell morphology/development ( J:116168 )

• bone marrow shows a predominance of segmented cells and a decrease in the proportion of red cells and lymphocytes

increased granulocyte number ( J:116168 )

• granulocytosis is seen in 8 week old mutants which progresses with age

• bone marrow shows an increase of CD11b+ granulocyte lineage at 16 weeks

decreased lymphocyte cell number ( J:116168 )

• severe lymphopenia is seen in 8 week old mutants which progresses with age

• however, no changes in platelet number or volume are seen

decreased B cell number ( J:116168 )

• bone marrow shows a reduction of B cells at 16 weeks of age

• progressive age-related reduction in the percentage of B cells in the lymph nodes and Peyers patches

• both at 16 and 28 weeks of age, B cells in the periarteriolar sheath of the spleen are reduced

• at 28 weeks of age, B cells are decreased to 25% of the normal number in the spleen

• peripheral blood shows a reduction of B220+ cells

decreased follicular B cell number ( J:116168 )

• slight reduction in the number of B220+ cells in the spleen of 8 week old mice, with a severe reduction in the area containing follicular B cells (B220+) from 16 weeks of age

decreased marginal zone B cell number ( J:116168 )

• the marginal zone compartment is smaller in the spleen of 16 week old mice

increased monocyte cell number ( J:116168 )

• bone marrow shows an increase of monocyte lineages at 16 weeks

abnormal alpha-beta T cell morphology ( J:116168 )

• more than 50% reduction of CD4+, and CD8+ cells in the spleen

• increase in the percentage of CD4+ and CD8+ cells in the lymph nodes and Peyers patches

• peripheral blood shows a reduction of CD4+ and CD8+ cells

abnormal spleen morphology ( J:116168 )

• at 36 weeks of age, spleen is almost entirely hematopoietic and mainly composed of erythroid tissue

enlarged spleen ( J:116168 )

• spleens of 16 week old mice are enlarged and are greatly swollen at 36 weeks of age

increased spleen red pulp amount ( J:116168 )

• increase of red pulp in the spleen of 16 week old mice

decreased spleen white pulp amount ( J:116168 )

• decrease of white pulp in the spleen of 16 week old mice, with white pulp greatly diminished at 36 weeks of age

increased IgA level ( J:116168 )

• IgA deposits within the mesangium

immune system

colitis ( J:116168 )

• 3 of 7 and 4 of 5 mice show indications of ulcerative colitis at 8 weeks and 16 weeks of age, respectively

• all mice exhibit severe colitis aggravated by fibrosis and mucosal pseudopolyposis at 36 weeks of age

abnormal thymus morphology ( J:116168 )

• cellularity of thymus is slightly reduced in 8 week old mutants

• however, no alterations in the cortex and medulla are seen

decreased thymus weight ( J:116168 )

• weight of thymus is slightly reduced in 8 week old mutants

abnormal lymphopoiesis ( J:116168 )

• bone marrow lymphopoiesis is deficient

increased granulocyte number ( J:116168 )

• granulocytosis is seen in 8 week old mutants which progresses with age

• bone marrow shows an increase of CD11b+ granulocyte lineage at 16 weeks

decreased lymphocyte cell number ( J:116168 )

• severe lymphopenia is seen in 8 week old mutants which progresses with age

• however, no changes in platelet number or volume are seen

decreased B cell number ( J:116168 )

• bone marrow shows a reduction of B cells at 16 weeks of age

• progressive age-related reduction in the percentage of B cells in the lymph nodes and Peyers patches

• both at 16 and 28 weeks of age, B cells in the periarteriolar sheath of the spleen are reduced

• at 28 weeks of age, B cells are decreased to 25% of the normal number in the spleen

• peripheral blood shows a reduction of B220+ cells

decreased follicular B cell number ( J:116168 )

• slight reduction in the number of B220+ cells in the spleen of 8 week old mice, with a severe reduction in the area containing follicular B cells (B220+) from 16 weeks of age

decreased marginal zone B cell number ( J:116168 )

• the marginal zone compartment is smaller in the spleen of 16 week old mice

increased monocyte cell number ( J:116168 )

• bone marrow shows an increase of monocyte lineages at 16 weeks

abnormal alpha-beta T cell morphology ( J:116168 )

• more than 50% reduction of CD4+, and CD8+ cells in the spleen

• increase in the percentage of CD4+ and CD8+ cells in the lymph nodes and Peyers patches

• peripheral blood shows a reduction of CD4+ and CD8+ cells

abnormal spleen morphology ( J:116168 )

• at 36 weeks of age, spleen is almost entirely hematopoietic and mainly composed of erythroid tissue

enlarged spleen ( J:116168 )

• spleens of 16 week old mice are enlarged and are greatly swollen at 36 weeks of age

increased spleen red pulp amount ( J:116168 )

• increase of red pulp in the spleen of 16 week old mice

decreased spleen white pulp amount ( J:116168 )

• decrease of white pulp in the spleen of 16 week old mice, with white pulp greatly diminished at 36 weeks of age

increased IgA level ( J:116168 )

• IgA deposits within the mesangium

abnormal Peyer's patch T cell area morphology ( J:116168 )

• increase in the percentage of CD4+ and CD8+ cells in the Peyers patches

abnormal lymph node B cell domain morphology ( J:116168 )

• at 16 weeks of age, the B-lymphoid cortical zone of lymph nodes is thinner

increased autoantibody level ( J:116168 )

• serum contains antibodies specific for nuclear and/or cytoplasmic antigens

joint inflammation ( J:116168 )

• 1/3 of mice show inflammation of the hip and knee joints at 36 weeks of age

glomerulonephritis ( J:116168 )

• mesangial proliferative glomerulonephritis with focal and segmental alternations becomes evident at 8 weeks of age

• glomerular lesions consist of increased mesangial matrix and mesangial hypercellularity that are mild at 8 weeks, moderate and severe at 16 weeks

lung inflammation ( J:116168 )

• all mice exhibit interstitial inflammation in the lungs at 16 and 36 weeks of age, confined to the walls of alveoli

interstitial pneumonia ( J:116168 )

• signs of hypersensitive pneumonitis, usually centered on bronchioles, is seen in 5/11 mice at 16-36 weeks of age

renal/urinary system

glomerulonephritis ( J:116168 )

• mesangial proliferative glomerulonephritis with focal and segmental alternations becomes evident at 8 weeks of age

• glomerular lesions consist of increased mesangial matrix and mesangial hypercellularity that are mild at 8 weeks, moderate and severe at 16 weeks

abnormal glomerular mesangium morphology ( J:116168 )

• diffuse, arborized granular deposits within the mesangium are composed of IgA, in combination with small amounts of IgG

glomerulosclerosis ( J:116168 )

• occasional segmental sclerosis and hyalinosis

respiratory system

lung inflammation ( J:116168 )

• all mice exhibit interstitial inflammation in the lungs at 16 and 36 weeks of age, confined to the walls of alveoli

interstitial pneumonia ( J:116168 )

• signs of hypersensitive pneumonitis, usually centered on bronchioles, is seen in 5/11 mice at 16-36 weeks of age

skeleton

joint inflammation ( J:116168 )

• 1/3 of mice show inflammation of the hip and knee joints at 36 weeks of age

growth/size/body

enlarged spleen ( J:116168 )

• spleens of 16 week old mice are enlarged and are greatly swollen at 36 weeks of age