Phenotypes associated with this allele

• Allele Symbol: Spib^tm1Mcs
• Allele Name: targeted mutation 1, M Celeste Simon
• Allele ID: MGI:2448991
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S1/Sv * 129X1/SvJ	MGI:4430083
hm2	Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2654536
cx3	Spi1^tm1Sing/Spi1^+ Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S/SvEv * 129X1/SvJ	MGI:3609010
cx4	Spi1^tm1Sing/Spi1^tm1Sing Spib^tm1Mcs/Spib^tm1Mcs	involves: 129S/SvEv * 129X1/SvJ	MGI:3609211
cx5	Spi1^tm1Sing/Spi1^+ Spib^tm1Mcs/Spib^+	involves: 129S/SvEv * 129X1/SvJ	MGI:3609212

Genotype
MGI:4430083

hm1

• Allelic Composition: Spib^tm1Mcs/Spib^tm1Mcs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

immune system

increased B cell apoptosis ( J:45245 )

• increase in apoptosis of splenic B cells after immunization

decreased B cell proliferation ( J:45245 )

• B cells proliferate poorly and die in response to IgM stimulation, but respond normally to lipopolysaccharide stimulation

abnormal spleen white pulp morphology ( J:45245 )

• follicular zonation separating the germinal center, mantle zone and marginal zone are abnormal

abnormal spleen B cell follicle morphology ( J:45245 )

• following T-dependent antigenic challenge, spleens contain more B220+ B cells outside of the white pulp, indicating deterioration of the follicular organization

abnormal spleen germinal center morphology ( J:45245 )

• mutants fail to maintain their germinal centers following T-dependent antigenic challenge; germinal centers are smaller and are mostly eliminated as early as 21 days after antigenic challenge with increased numbers of apoptotic B cells

abnormal humoral immune response ( J:45245 )

• abnormal humoral immune responses to DNP-KLH

decreased IgG1 level ( J:45245 )

• secondary responses to T-dependent antigen show 3- to 5-fold lower levels of IgG1 8 days after reimmunization

decreased IgG2a level ( J:45245 )

• mutants immunized with a T-dependent antigen have lower serum antigen-specific IgG2a levels

• secondary responses show a 35-fold reduction in IgG2a levels after reimmunization

decreased IgG2b level ( J:45245 )

• secondary responses to T-dependent antigen show a 35-fold reduction in IgG2b levels 8 days after reimmunization

increased IgM level ( J:45245 )

• mutants immunized with a T-dependent antigen have 14-fold higher serum antigen-specific IgM levels

hematopoietic system

increased B cell apoptosis ( J:45245 )

• increase in apoptosis of splenic B cells after immunization

decreased B cell proliferation ( J:45245 )

• B cells proliferate poorly and die in response to IgM stimulation, but respond normally to lipopolysaccharide stimulation

abnormal spleen white pulp morphology ( J:45245 )

• follicular zonation separating the germinal center, mantle zone and marginal zone are abnormal

abnormal spleen B cell follicle morphology ( J:45245 )

• following T-dependent antigenic challenge, spleens contain more B220+ B cells outside of the white pulp, indicating deterioration of the follicular organization

abnormal spleen germinal center morphology ( J:45245 )

• mutants fail to maintain their germinal centers following T-dependent antigenic challenge; germinal centers are smaller and are mostly eliminated as early as 21 days after antigenic challenge with increased numbers of apoptotic B cells

decreased IgG1 level ( J:45245 )

• secondary responses to T-dependent antigen show 3- to 5-fold lower levels of IgG1 8 days after reimmunization

decreased IgG2a level ( J:45245 )

• mutants immunized with a T-dependent antigen have lower serum antigen-specific IgG2a levels

• secondary responses show a 35-fold reduction in IgG2a levels after reimmunization

decreased IgG2b level ( J:45245 )

• secondary responses to T-dependent antigen show a 35-fold reduction in IgG2b levels 8 days after reimmunization

increased IgM level ( J:45245 )

• mutants immunized with a T-dependent antigen have 14-fold higher serum antigen-specific IgM levels

cellular

increased B cell apoptosis ( J:45245 )

• increase in apoptosis of splenic B cells after immunization

decreased B cell proliferation ( J:45245 )

• B cells proliferate poorly and die in response to IgM stimulation, but respond normally to lipopolysaccharide stimulation

Genotype
MGI:2654536

hm2

• Allelic Composition: Spib^tm1Mcs/Spib^tm1Mcs
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

hematopoietic 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 immature B cell morphology ( J:88257 )

• 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

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 immature B cell morphology ( J:88257 )

• 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

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

Genotype
MGI:3609010

cx3

• 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 )

• total numbers of B cells is reduced

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

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

cx4

• 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

cx5

• 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