Phenotypes associated with this allele

• Allele Symbol: Blnk^tm1Kplm
• Allele Name: targeted mutation 1, Kong-Peng Lam
• Allele ID: MGI:2386672
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Blnk^tm1Kplm/Blnk^tm1Kplm	involves: 129P2/OlaHsd	MGI:3844028
cx2	Blnk^tm1Kplm/Blnk^tm1Kplm Igh^tm4Cgn/Igh^+ Igk^tm1Rsky/Igk^+	involves: 129P2/OlaHsd	MGI:3844072
cx3	Blnk^tm1Kplm/Blnk^tm1Kplm Plcg2^tm1.1Kuro/Plcg2^tm1.1Kuro	involves: 129P2/OlaHsd	MGI:3844213
cx4	Blnk^tm1Kplm/Blnk^tm1Kplm Plcg2^tm1.1Kuro/Plcg2^+	involves: 129P2/OlaHsd	MGI:3844214

Genotype
MGI:3844028

hm1

• Allelic Composition: Blnk^tm1Kplm/Blnk^tm1Kplm
• Genetic Background: involves: 129P2/OlaHsd

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

immune system

increased B cell apoptosis ( J:131161 )

• B cells in culture have about a 20% rate of death after 4-6 hours

abnormal B cell differentiation ( J:61130 , J:131161 )

• there is a severe inhibition in the transition from pre-B cell to pro-B cell (J:61130)

• cell development is partially blocked at an early transition stage before the small pre-B cell stage, most likely at the late pro-B or large pre-B cell stage (J:131161)

• evidence includes a low number of peripheral B cells, an increase percentage of B220⁺ IgL^- cells and a 50-fold increase in the number of marrow cells expressing pre-BCR (J:131161)

decreased immature B cell number ( J:61130 )

• there is a 3-fold drop in immature B220⁺ IgM⁺ B cell numbers found in the bone marrow

increased pro-B cell number ( J:61130 , J:131161 )

• there is a 2-fold accumulation of pro-B cell numbers found in the bone marrow (J:61130)

• there is in increase in B220⁺ IgL^- cells in the bone marrow (J:131161)

decreased B cell number ( J:61130 , J:131161 )

• three week old mice have a 30-fold drop in splenic B cells compared to controls (J:61130)

• 6 and 12 week old mice have B cell numbers reduced by 7- and 2- fold, respectively (J:61130)

• B cell numbers in the spleen are reduced 90% compared to wild-type controls (J:131161)

decreased mature B cell number ( J:61130 )

• there is a 2- to 4- fold drop in the recirculating mature B220^high IgM^low B cell numbers found in the bone marrow

• IgM^low IgD^high mature B cells are severely reduced in in the spleen by 7-fold and are not found in the lymph nodes

absent B-1a cells ( J:61130 )

• B-1a B cells are not found in the peritoneal cavity of 3-month old mice

decreased pre-B cell number ( J:61130 , J:120460 )

• there is a 5-fold drop in pre-B cell numbers found in the bone marrow (J:61130)

• pre- B cell numbers are severely reduced in the bone marrow (J:120460)

spleen hypoplasia ( J:131161 )

• spleen cellularity is about one quarter of that in wild-type mice

abnormal B cell activation ( J:61130 , J:131161 )

• B cells fail to upregulate CD69 and CD86 in response to anti-IgM stimulation (J:61130)

• B cells fail to produce IgM or IgG3 immunoglobulins in response to T cell independent antigens (J:61130)

• normal levels of immunoglobulin are produced to T cell dependent antigens (J:61130)

• there is a 4.3 fold decrease in the concentration of calcium fluxed intracellularly after stimulus compared to wild-type controls (J:131161)

decreased B cell proliferation ( J:61130 )

• B cells fail to upregulate activation markers or proliferate in response to anti-IgM stimulation

hematopoietic system

increased B cell apoptosis ( J:131161 )

• B cells in culture have about a 20% rate of death after 4-6 hours

abnormal B cell differentiation ( J:61130 , J:131161 )

• there is a severe inhibition in the transition from pre-B cell to pro-B cell (J:61130)

• cell development is partially blocked at an early transition stage before the small pre-B cell stage, most likely at the late pro-B or large pre-B cell stage (J:131161)

• evidence includes a low number of peripheral B cells, an increase percentage of B220⁺ IgL^- cells and a 50-fold increase in the number of marrow cells expressing pre-BCR (J:131161)

decreased immature B cell number ( J:61130 )

• there is a 3-fold drop in immature B220⁺ IgM⁺ B cell numbers found in the bone marrow

increased pro-B cell number ( J:61130 , J:131161 )

• there is a 2-fold accumulation of pro-B cell numbers found in the bone marrow (J:61130)

• there is in increase in B220⁺ IgL^- cells in the bone marrow (J:131161)

decreased B cell number ( J:61130 , J:131161 )

• three week old mice have a 30-fold drop in splenic B cells compared to controls (J:61130)

• 6 and 12 week old mice have B cell numbers reduced by 7- and 2- fold, respectively (J:61130)

• B cell numbers in the spleen are reduced 90% compared to wild-type controls (J:131161)

decreased mature B cell number ( J:61130 )

• there is a 2- to 4- fold drop in the recirculating mature B220^high IgM^low B cell numbers found in the bone marrow

• IgM^low IgD^high mature B cells are severely reduced in in the spleen by 7-fold and are not found in the lymph nodes

absent B-1a cells ( J:61130 )

• B-1a B cells are not found in the peritoneal cavity of 3-month old mice

decreased pre-B cell number ( J:61130 , J:120460 )

• there is a 5-fold drop in pre-B cell numbers found in the bone marrow (J:61130)

• pre- B cell numbers are severely reduced in the bone marrow (J:120460)

spleen hypoplasia ( J:131161 )

• spleen cellularity is about one quarter of that in wild-type mice

abnormal B cell activation ( J:61130 , J:131161 )

• B cells fail to upregulate CD69 and CD86 in response to anti-IgM stimulation (J:61130)

• B cells fail to produce IgM or IgG3 immunoglobulins in response to T cell independent antigens (J:61130)

• normal levels of immunoglobulin are produced to T cell dependent antigens (J:61130)

• there is a 4.3 fold decrease in the concentration of calcium fluxed intracellularly after stimulus compared to wild-type controls (J:131161)

decreased B cell proliferation ( J:61130 )

• B cells fail to upregulate activation markers or proliferate in response to anti-IgM stimulation

cellular

increased B cell apoptosis ( J:131161 )

• B cells in culture have about a 20% rate of death after 4-6 hours

decreased B cell proliferation ( J:61130 )

• B cells fail to upregulate activation markers or proliferate in response to anti-IgM stimulation

Genotype
MGI:3844072

cx2

• Allelic Composition: Blnk^tm1Kplm/Blnk^tm1Kplm; Igh^tm4Cgn/Igh⁺; Igk^tm1Rsky/Igk⁺
• Genetic Background: involves: 129P2/OlaHsd

immune system

abnormal B cell differentiation ( J:120460 )

• innocuous transgenic BCR on Blnk null B cells leads to enhanced development of these B cells compared to Blnk homozygotes

• two populations are detected in the bone marrow consisting of IgM^lo and IgM^hi groups

• both populations appear to be immature B cells as they have low surface level expression of MHC-II and CD43, and high levels of CD24

• based on intensity of these surface markers, the IgM^lo population is the less mature of the two

• in vitro maturation of bone marrow cells demonstrate delayed development of these IgM⁺ cells

• B cells in the periphery are primarily T1 stage B cells that have a short half-life

increased transitional stage B cell number ( J:120460 )

• B cells in the periphery are primarily T1 stage B cells

decreased B cell number ( J:120460 )

• B cell numbers are decreased 2- to 3- fold in the spleen

• the B cells present are primarily T1 stage B cells

increased pre-B cell number ( J:120460 )

• pre-B cell numbers are 2-3 fold higher in the bone marrow than in transgenic controls

hematopoietic system

abnormal B cell differentiation ( J:120460 )

• innocuous transgenic BCR on Blnk null B cells leads to enhanced development of these B cells compared to Blnk homozygotes

• two populations are detected in the bone marrow consisting of IgM^lo and IgM^hi groups

• both populations appear to be immature B cells as they have low surface level expression of MHC-II and CD43, and high levels of CD24

• based on intensity of these surface markers, the IgM^lo population is the less mature of the two

• in vitro maturation of bone marrow cells demonstrate delayed development of these IgM⁺ cells

• B cells in the periphery are primarily T1 stage B cells that have a short half-life

increased transitional stage B cell number ( J:120460 )

• B cells in the periphery are primarily T1 stage B cells

decreased B cell number ( J:120460 )

• B cell numbers are decreased 2- to 3- fold in the spleen

• the B cells present are primarily T1 stage B cells

increased pre-B cell number ( J:120460 )

• pre-B cell numbers are 2-3 fold higher in the bone marrow than in transgenic controls

Genotype
MGI:3844213

cx3

• Allelic Composition: Blnk^tm1Kplm/Blnk^tm1Kplm; Plcg2^tm1.1Kuro/Plcg2^tm1.1Kuro
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

perinatal lethality, incomplete penetrance ( J:131161 )

• many mice have perinatal deaths due to a bleeding disorder associated with PLCgamma-2 deficiency

• at weaning, litters from double heterozygote parents only yielded 1 out of 40 pups that were double homozygotes

immune system

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 60% after 4 hours and 80% dead after six hours

decreased B cell number ( J:131161 )

• B cell lineage cells are reduced 3- to 5-fold compared to mice null homozygotes for just one of the alleles

• splenic B cell numbers are reduced to 4.1% of lymphocytes

spleen hypoplasia ( J:131161 )

• spleen cellularity is about one half of that in wild-type mice

hematopoietic system

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 60% after 4 hours and 80% dead after six hours

decreased B cell number ( J:131161 )

• B cell lineage cells are reduced 3- to 5-fold compared to mice null homozygotes for just one of the alleles

• splenic B cell numbers are reduced to 4.1% of lymphocytes

spleen hypoplasia ( J:131161 )

• spleen cellularity is about one half of that in wild-type mice

cellular

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 60% after 4 hours and 80% dead after six hours

Genotype
MGI:3844214

cx4

• Allelic Composition: Blnk^tm1Kplm/Blnk^tm1Kplm; Plcg2^tm1.1Kuro/Plcg2⁺
• Genetic Background: involves: 129P2/OlaHsd

immune system

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 50% after 4 hours and 70% dead after 6 hours

decreased B cell number ( J:131161 )

• splenic B cell numbers are reduced to 13.5% of lymphocytes

abnormal B cell activation ( J:131161 )

• there is a 4.3 fold decrease in the concentration of calcium fluxed intracellularly after stimulus compared to wild-type controls

hematopoietic system

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 50% after 4 hours and 70% dead after 6 hours

decreased B cell number ( J:131161 )

• splenic B cell numbers are reduced to 13.5% of lymphocytes

abnormal B cell activation ( J:131161 )

• there is a 4.3 fold decrease in the concentration of calcium fluxed intracellularly after stimulus compared to wild-type controls

cellular

increased B cell apoptosis ( J:131161 )

• 40% of B cells are dead after 2 hours in culture with 50% after 4 hours and 70% dead after 6 hours