Phenotypes associated with this allele

• Allele Symbol: Dock2^m1Hsd
• Allele Name: mutation 1, Harlan
• Allele ID: MGI:5319388
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Cmah^tm1Avrk/Cmah^tm1Avrk Dock2^m1Hsd/Dock2^m1Hsd	B6NHsd.Cg-Dock2^m1Hsd Cmah^tm1Avrk	MGI:3830715
cx2	Dock2^m1Hsd/Dock2^m1Hsd Irf5^tm1Ttg/Irf5^tm1Ttg	B6NHsd.Cg-Irf5^tm1Ttg Dock2^m1Hsd	MGI:5319391
cx3	Dock2^m1Hsd/Dock2^m1Hsd Siae^tm1.2Avrk/Siae^tm1.2Avrk	B6NHsd.Cg-Siae^tm1.2Avrk Dock2^m1Hsd	MGI:3830712
cx4	Cmah^tm1Avrk/Cmah^tm1Avrk Dock2^m1Hsd/Dock2^m1Hsd Siae^tm1.2Avrk/Siae^tm1.2Avrk	B6NHsd.Cg-Siae^tm1.2Avrk Dock2^m1Hsd Cmah^tm1Avrk	MGI:3830714

Genotype
MGI:3830715

cx1

• Allelic Composition: Cmah^tm1Avrk/Cmah^tm1Avrk; Dock2^m1Hsd/Dock2^m1Hsd
• Genetic Background: B6NHsd.Cg-Dock2^m1Hsd Cmah^tm1Avrk

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

immune system

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells are severely reduced in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells

hematopoietic system

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells are severely reduced in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells

behavior/neurological

abnormal startle reflex ( J:122351 )

• abnormal startle response to acoustic stimuli; higher acoustic stimuli is required to increase startle response compared to controls with mutants showing a lower response to stimuli between 82 and 118 dB

impaired coordination ( J:122351 )

• mice show impaired coordination in the rotarod test in 1- and 3-day protocols

increased vertical activity ( J:122351 )

• in open field, vertical activity is increased

hearing/vestibular/ear

abnormal inner ear morphology ( J:122351 )

abnormal cochlear sensory epithelium morphology ( J:122351 )

• 9-month old mice have sensory epithelium abnormalities of the vestibular and auditory inner ear

abnormal organ of Corti morphology ( J:122351 )

• outer hair cell degeneration occurs with collapse of the outer organ of Corti in the basal turn

cochlear outer hair cell degeneration ( J:122351 )

• some mice exhibit degeneration throughout the cochlea

abnormal semicircular canal morphology ( J:122351 )

• semicircular canal organs show defects, albeit more subtle, similar to the acellular deposits on the vestibular otoconial epithelia

abnormal otolithic membrane morphology ( J:122351 )

• deposits of acellular material are present on the apical surface of the vestibular otoconial epithelia

impaired hearing ( J:122351 )

• at 9 months, mice have reduced hearing sensitivity across frequencies

homeostasis/metabolism

impaired wound healing ( J:122351 )

• wound repair is markedly delayed in mutants compared to wild-type mice, most noticeable in rate of wound closure between period of 4-9 days after wounding

nervous system

cochlear outer hair cell degeneration ( J:122351 )

• some mice exhibit degeneration throughout the cochlea

abnormal sensorimotor gating ( J:122351 )

• abnormal sensorimotor gating is exhibited

Genotype
MGI:5319391

cx2

• Allelic Composition: Dock2^m1Hsd/Dock2^m1Hsd; Irf5^tm1Ttg/Irf5^tm1Ttg
• Genetic Background: B6NHsd.Cg-Irf5^tm1Ttg Dock2^m1Hsd

immune system

abnormal B cell differentiation ( J:182658 )

• mice exhibit impaired B cell and plasmacytoid dendritic cell development compared with wild-type mice

• however, expression of Dock2 rescues B cell and plasmacytoid dendritic cell development

increased immature B cell number ( J:182658 )

decreased plasmacytoid dendritic cell number ( J:182658 )

• sharp reduction in the spleen (8.7-fold) and blood (6.2-fold)

• reduced percentage to total leukocytes in the peripheral blood

increased plasmacytoid dendritic cell number ( J:182658 )

• slight increase in frequency and number in the bone marrow

decreased follicular B cell number ( J:182658 )

• 3.8-fold

absent marginal zone B cells ( J:182658 )

• virtually absent

increased B cell number ( J:182658 )

• in the blood

decreased splenocyte number ( J:182658 )

• frequency (3.1-fold) and number (1.3-fold) at 8 weeks

decreased interferon-alpha secretion ( J:182658 )

• from plasmacytoid dendritic cell stimulated with CpG-A

abnormal response to infection ( J:182658 )

• mice exhibit reduced (7-fold at day 6 and 43-fold at day 9) specific IgG titers compared with wild-type mice

hematopoietic system

abnormal B cell differentiation ( J:182658 )

• mice exhibit impaired B cell and plasmacytoid dendritic cell development compared with wild-type mice

• however, expression of Dock2 rescues B cell and plasmacytoid dendritic cell development

increased immature B cell number ( J:182658 )

decreased plasmacytoid dendritic cell number ( J:182658 )

• sharp reduction in the spleen (8.7-fold) and blood (6.2-fold)

• reduced percentage to total leukocytes in the peripheral blood

increased plasmacytoid dendritic cell number ( J:182658 )

• slight increase in frequency and number in the bone marrow

decreased follicular B cell number ( J:182658 )

• 3.8-fold

absent marginal zone B cells ( J:182658 )

• virtually absent

increased B cell number ( J:182658 )

• in the blood

decreased splenocyte number ( J:182658 )

• frequency (3.1-fold) and number (1.3-fold) at 8 weeks

Genotype
MGI:3830712

cx3

• Allelic Composition: Dock2^m1Hsd/Dock2^m1Hsd; Siae^tm1.2Avrk/Siae^tm1.2Avrk
• Genetic Background: B6NHsd.Cg-Siae^tm1.2Avrk Dock2^m1Hsd

Glomerulonephritis in Siae^tm1.2Avrk/Siae^tm1.2Avrk mice

immune system

decreased B-1a cell number ( J:144035 )

• the percentage of B1a B cells in the peritoneum is reduced by about half

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 , J:231437 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells, are severely reduced in the spleen compared to controls (J:144035)

• MZP B cells are reduced 10.5 fold and MZ B cells are reduced 23 fold compared to controls (J:144035)

• Background Sensitivity: unlike mice bred to a C57BL/6J background for an additional 13 generation, mice bred to a C57BL/6NHsd background for only 10 generations exhibit loss of marginal zone B cells compared with wild-type mice (J:231437)

increased B-1b cell number ( J:144035 )

• the percentage of B1b B cells in the peritoneum is increased by over half

increased CD4-positive, alpha-beta memory T cell number ( J:231437 )

• Background Sensitivity: unlike mice bred to a C57BL/6J background for an additional 13 generation, mice bred to a C57BL/6NHsd background for only 10 generations exhibit an increase in memory T cells in blood and spleen compared with wild-type mice

decreased T cell number ( J:144035 )

• T cell numbers are slightly reduced in the thymus and almost 2-fold reduced in the spleen

spleen hypoplasia ( J:144035 )

• there is a 2.4 fold decrease in the number of cells in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells

increased B cell proliferation ( J:144035 )

• B cells proliferate faster than controls with sub-optimal doses of anti-IgM

• the proliferation advantage is diminished with higher doses and/or longer stimulation times possibly from increased rates of apoptosis

abnormal immunoglobulin level ( J:144035 )

increased IgE level ( J:144035 )

• IgE levels are significantly higher than in controls

increased IgG1 level ( J:144035 )

• IgG1 levels are significantly higher than in controls

increased IgG2a level ( J:144035 )

• lower levels of antigen-specific IgG2a are present after immunization

increased IgG2b level ( J:144035 )

• IgG2b levels are significantly higher than in controls

• however, lower levels of antigen-specific IgG2b are present after immunization

increased IgG3 level ( J:144035 )

• lower levels of antigen-specific IgG3 are present after immunization

increased IgM level ( J:144035 )

• IgM levels are significantly higher than in controls

increased anti-double stranded DNA antibody level ( J:144035 )

• higher levels of anti-DS DNA antibodies than in controls are found in the sera of mice 20-60 weeks of age

increased anti-histone antibody level ( J:144035 )

• higher levels of anti-histone antibodies than in controls are found in the sera of mice 20-60 weeks of age

increased anti-single stranded DNA antibody level ( J:144035 )

• higher levels of anti-SS DNA antibodies than in controls are found in the sera of mice 20-60 weeks of age

glomerulonephritis ( J:144035 )

• mutants develop an immune complex-glomerulonephritis

hematopoietic system

decreased B-1a cell number ( J:144035 )

• the percentage of B1a B cells in the peritoneum is reduced by about half

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 , J:231437 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells, are severely reduced in the spleen compared to controls (J:144035)

• MZP B cells are reduced 10.5 fold and MZ B cells are reduced 23 fold compared to controls (J:144035)

• Background Sensitivity: unlike mice bred to a C57BL/6J background for an additional 13 generation, mice bred to a C57BL/6NHsd background for only 10 generations exhibit loss of marginal zone B cells compared with wild-type mice (J:231437)

increased B-1b cell number ( J:144035 )

• the percentage of B1b B cells in the peritoneum is increased by over half

increased CD4-positive, alpha-beta memory T cell number ( J:231437 )

• Background Sensitivity: unlike mice bred to a C57BL/6J background for an additional 13 generation, mice bred to a C57BL/6NHsd background for only 10 generations exhibit an increase in memory T cells in blood and spleen compared with wild-type mice

decreased T cell number ( J:144035 )

• T cell numbers are slightly reduced in the thymus and almost 2-fold reduced in the spleen

spleen hypoplasia ( J:144035 )

• there is a 2.4 fold decrease in the number of cells in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells

increased B cell proliferation ( J:144035 )

• B cells proliferate faster than controls with sub-optimal doses of anti-IgM

• the proliferation advantage is diminished with higher doses and/or longer stimulation times possibly from increased rates of apoptosis

abnormal immunoglobulin level ( J:144035 )

increased IgE level ( J:144035 )

• IgE levels are significantly higher than in controls

increased IgG1 level ( J:144035 )

• IgG1 levels are significantly higher than in controls

increased IgG2a level ( J:144035 )

• lower levels of antigen-specific IgG2a are present after immunization

increased IgG2b level ( J:144035 )

• IgG2b levels are significantly higher than in controls

• however, lower levels of antigen-specific IgG2b are present after immunization

increased IgG3 level ( J:144035 )

• lower levels of antigen-specific IgG3 are present after immunization

increased IgM level ( J:144035 )

• IgM levels are significantly higher than in controls

renal/urinary system

glomerulonephritis ( J:144035 )

• mutants develop an immune complex-glomerulonephritis

renal glomerular immunoglobulin deposits ( J:144035 )

cellular

increased B cell proliferation ( J:144035 )

• B cells proliferate faster than controls with sub-optimal doses of anti-IgM

• the proliferation advantage is diminished with higher doses and/or longer stimulation times possibly from increased rates of apoptosis

Genotype
MGI:3830714

cx4

• Allelic Composition: Cmah^tm1Avrk/Cmah^tm1Avrk; Dock2^m1Hsd/Dock2^m1Hsd; Siae^tm1.2Avrk/Siae^tm1.2Avrk
• Genetic Background: B6NHsd.Cg-Siae^tm1.2Avrk Dock2^m1Hsd Cmah^tm1Avrk

immune system

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells, are severely reduced in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells

hematopoietic system

decreased follicular B cell number ( J:144035 )

• there is a selective loss of recirculating follicular phenotype B cells from the perisinusoidal niche of bone marrow

decreased marginal zone B cell number ( J:144035 )

• numbers of IgM^hiIgD^hiCD21^hiMZ B cell precursors (MZP), as well as IgM^hiIgD^lowCD21^hiMZ B cells, are severely reduced in the spleen compared to controls

abnormal B cell activation ( J:144035 )

• splenic B cells stimulated with anti-IgM have enhanced calcium influx

• enhanced calcium influx was observed for newly formed B cells, follicular B cells, and marginal zone B cells