Phenotypes associated with this allele

• Allele Symbol: Spi1^tm1Sing
• Allele Name: targeted mutation 1, Harinder Singh
• Allele ID: MGI:1930970
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spi1^tm1Sing/Spi1^tm1Sing	involves: 129S/SvEv	MGI:3583365
cx2	Spi1^tm1Sing/Spi1^+ Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S/SvEv * 129X1/SvJ	MGI:3609010
cx3	Spi1^tm1Sing/Spi1^tm1Sing Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S/SvEv * 129X1/SvJ	MGI:3609211
cx4	Spi1^tm1Sing/Spi1^+ Spib^tm1Mcs/Spib^+	involves: 129S/SvEv * 129X1/SvJ	MGI:3609212

Genotype
MGI:3583365

hm1

• Allelic Composition: Spi1^tm1Sing/Spi1^tm1Sing
• Genetic Background: involves: 129S/SvEv

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:20348 , J:138501 )

• fetuses die between E16.5 and E18 (J:20348)

• mice are present at E14.5 but are dead at birth (J:138501)

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:138501 )

• fetal liver progenitor cells form fewer colonies when cultured with granulocyte-colony stimulating factor, macrophage colony stimulating factor or IL3, IL6 and stem cell factor compared to fetal liver cells from wild-type mice

• after several passages, fetal liver cells grow faster than wild-type cells in culture and resemble immature blast cells instead of immature mast cells

abnormal erythropoiesis ( J:20348 )

• normal numbers of megakaryocytes and erythroid progenitors

• impaired maturation of fetal erythroblasts

abnormal leukopoiesis ( J:20348 )

• impaired generation of leukocyte progenitors

abnormal B cell differentiation ( J:20348 )

abnormal T cell differentiation ( J:20348 )

anemia ( J:20348 )

decreased hematocrit ( J:20348 )

abnormal granulocyte morphology ( J:20348 )

abnormal monocyte morphology ( J:20348 )

immune system

abnormal leukopoiesis ( J:20348 )

• impaired generation of leukocyte progenitors

abnormal B cell differentiation ( J:20348 )

abnormal T cell differentiation ( J:20348 )

abnormal granulocyte morphology ( J:20348 )

abnormal monocyte morphology ( J:20348 )

Genotype
MGI:3609010

cx2

• Allelic Composition: Spi1^tm1Sing/Spi1⁺; Spib^tm1Mcs/Spib^tm1Mcs
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ

hematopoietic system

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased

abnormal B cell differentiation ( J:88257 )

abnormal immature B cell morphology ( J:88257 )

• decreased bone marrow B220^hi/int CD43^- IgM⁺ and B220^hi CD43^- HSA^lo B cells and normal B220^int CD43^- IgM^- and B220^hi CD43^- HSA^hi population indicating a deficiency in immature and mature B cells but normal levels of pro-B and pre-B cells

• E16.5 fetal liver has reduced numbers of B220⁺ CD43^- cells but normal numbers of B220⁺ CD43⁺ cells

• bone marrow has 50% fewer IgM⁺ IgD⁺ and IgM⁺ IgD^- B cells, and also decreased B220⁺ CD43^- B cells and B220⁺ BP-1⁺ B cells

• although B cells from bone marrow and periphery have normal Igl and Igk expression, splenic B cells have 2 to 4 fold higher surface expression of IgM and B cells also express high levels of surface CD19 and CD21

decreased B cell number ( J:88257 )

• B220⁺ IgM⁺ and IgM⁺ IgD⁺ B cells are decreased in number by 50% in spleen and 60%-80% in lymph node

• total numbers of B cells is reduced

absent spleen germinal center ( J:88257 )

• no peanut agglutinin positive germinal centers are found at 10 or 28 days post-immunization

immune system

immune system phenotype ( J:88257 )

N • myeloid lineages appear normal by flow cytometry

N • thymic CD4/CD8 profiles and splenic CD4/CD8 and TCRab/CD3 profiles are normal

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased

abnormal B cell differentiation ( J:88257 )

abnormal immature B cell morphology ( J:88257 )

• decreased bone marrow B220^hi/int CD43^- IgM⁺ and B220^hi CD43^- HSA^lo B cells and normal B220^int CD43^- IgM^- and B220^hi CD43^- HSA^hi population indicating a deficiency in immature and mature B cells but normal levels of pro-B and pre-B cells

• E16.5 fetal liver has reduced numbers of B220⁺ CD43^- cells but normal numbers of B220⁺ CD43⁺ cells

• bone marrow has 50% fewer IgM⁺ IgD⁺ and IgM⁺ IgD^- B cells, and also decreased B220⁺ CD43^- B cells and B220⁺ BP-1⁺ B cells

• although B cells from bone marrow and periphery have normal Igl and Igk expression, splenic B cells have 2 to 4 fold higher surface expression of IgM and B cells also express high levels of surface CD19 and CD21

decreased B cell number ( J:88257 )

• B220⁺ IgM⁺ and IgM⁺ IgD⁺ B cells are decreased in number by 50% in spleen and 60%-80% in lymph node

• total numbers of B cells is reduced

absent spleen germinal center ( J:88257 )

• no peanut agglutinin positive germinal centers are found at 10 or 28 days post-immunization

cellular

increased B cell apoptosis ( J:88257 )

• B220⁺ TUNEL<+> splenic lymphocytes are increased 4 times over normal levels

• Annexin A5^hi immature and mature B cells are increased 3 to 4 times over normal levels

• increased splenic B cell apoptosis is found after immunization with the T-dependent antigen DNP-KLH

decreased B cell proliferation ( J:88257 )

• defect in proliferation in response to anti-IgM stimulation is much more severe than in Sfpi1^tm1Sing wild-type Spib^tm1Mcs homozygotes

• 2 to 3 fold reduction in B cell response to LPS although response to PMA and ionomycin is normal and response to anti-CD40 and IL4 is normal

• IgM cross-linking or pervanadate/H₂0₂ stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

• normal levels of LYN, FYN, BLK, SYK, and BTK are found and in vitro kinase assays of enolase show normal kinase activity in B cells and BLNK, VAV, CD79A, and CD79B are expressed at normal levels with SYK co-precipitating with CD79, but tyrosine phosphorylation of BLNK and PLC gamma is decreased

Genotype
MGI:3609211

cx3

• Allelic Composition: Spi1^tm1Sing/Spi1^tm1Sing; Spib^tm1Mcs/Spib^tm1Mcs
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:88257 )

Genotype
MGI:3609212

cx4

• Allelic Composition: Spi1^tm1Sing/Spi1⁺; Spib^tm1Mcs/Spib⁺
• Genetic Background: involves: 129S/SvEv * 129X1/SvJ

hematopoietic system

hematopoietic system phenotype ( J:88257 )

N

decreased B cell proliferation ( J:88257 )

• IgM cross-linking or pervanadate/H202 stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

abnormal spleen germinal center morphology ( J:88257 )

• although the B cell profiles in spleen and lymph node are normal, there are small splenic germinal centers, and inability to maintain germinal centers

immune system

decreased B cell proliferation ( J:88257 )

• IgM cross-linking or pervanadate/H202 stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal

abnormal spleen germinal center morphology ( J:88257 )

• although the B cell profiles in spleen and lymph node are normal, there are small splenic germinal centers, and inability to maintain germinal centers

cellular

decreased B cell proliferation ( J:88257 )

• IgM cross-linking or pervanadate/H202 stimulation yields less than normal levels of tyrosine phosphorylation and IgM cross-linking also yields less calcium mobilization than normal