Overview

Also Known As:BLNK KO

These Blnk knock-out mice exhibit a reduction of splenocyte number and arrest of B lymphocyte development.

Donating Investigator

Andrew C Chan, Genentech

Genetic overview

Genetic Background	Generation

Blnk^tm1Achn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Blnk	B cell linker

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Research Applications

Mouse/Human Gene Homologs
Research Tools
Immunology, Inflammation and Autoimmunity Research

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of bone marrow-derived cell lysates. There is a 65% reduction of splenocyte number. Development of B lymphocytes is arrested at the B220+CD43+ progenitor B cell to B220+CD43- precursor B cell transition stage. The reduced number of mature peripheral B-cells results in diminished serum Ig levels in adult homozygous mice. Peritoneal CD5+IgM+ B-1a B-cell numbers are decreased. This mutant mouse strain may be useful in studies of agammaglobulinemia.

Development

A targeting vector containing a floxed PGK-neo cassette and Green Fluorescent Protein sequence was used to disrupt exon 1, which encodes amino acids 1-60 and the initiation codon. The construct was electroporated into 129X1/SvJ derived BL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Suggestions

None Available

Additional Information

Considerations for Choosing Controls

Selected References

Pappu R; Cheng AM; Li B; Gong Q; Chiu C; Griffin N; White M; Sleckman BP; Chan AC. 1999. Requirement for B cell linker protein (BLNK) in B cell development. Science 286(5446):1949-54PubMed: 10583957 MGI: J:58805

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Genetics

Blnk^tm1Achn

Allele Symbol: Blnk^tm1Achn

Allele Name	targeted mutation 1, Andrew C Chan
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	BLNK-
Gene Symbol and Name	Blnk, B cell linker
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	19
Molecular Note	Exon 1 was disrupted by homologous recombination of a construct containing GFP, a floxed neo gene, and a mutated start codon (ATC). While the GFP coding region was linked to its own Kozak sequence and start codon, fluorescence was undetected in splenocytes and bone marrow cells derived from heterozygous mutant mice. Immunoblot analysis on homozygote bone marrow cells failed to detect Blnk protein.
Mutations Made By	Andrew Chan, Genentech

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
- agammaglobulinemia
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B cell deficiency

Genotype: Blnk^tm1Achn related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B cell deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B cell deficiency
- Cancer Research
  - B cell deficiency
Mouse/Human Gene Homologs
- agammaglobulinemia

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Blnk^tm1Achn/Blnk⁺
involves: 129S4/SvJae * 129X1/SvJ * BALB/c * C3H * C57BL/6

cellular phenotype

decreased B cell proliferation
- following cross linking the frequency of cycling cells is reduced and the percentage of cells with greater than 2N DNA is increased

hematopoietic system phenotype

decreased B cell proliferation
- following cross linking the frequency of cycling cells is reduced and the percentage of cells with greater than 2N DNA is increased

immune system phenotype

decreased B cell proliferation
- following cross linking the frequency of cycling cells is reduced and the percentage of cells with greater than 2N DNA is increased

Genotype: Blnk^tm1Achn/Blnk^tm1Achn
involves: 129X1/SvJ

immune system phenotype

decreased immunoglobulin level

arrested B cell differentiation
- profound block in B cell development
- cells fail to progress efficiently from the immature stage to the transitional stage

decreased B-1a cell number

abnormal B cell differentiation
- splenic B cells are larger in size and express higher membrane IgM levels indicating a defect in maturation to the B220^hiIgM^loIgD^hi stage

abnormal mature B cell morphology
- the few IgM+ peripheral B cells that are present are larger in size compared to controls

absent B-1b cells
- absent from the spleen and peritoneum

increased pro-B cell number
- accumulate B220+CD43+ pro-B cells

decreased mature B cell number
- decrease in IgM+ peripheral B cells in the spleen and a marked reduction in B220^hiIgM+ and IgM^loIgD^hi B cells in the bone marrow and periphery, respectively
- older mice have increased numbers of B220+ IgM+ B cells compared to younger mice but the numbers are still more than 10 times lower than in age matched controls

decreased splenocyte number
- a 65% reduction in splenocyte numbers

hematopoietic system phenotype

abnormal mature B cell morphology
- the few IgM+ peripheral B cells that are present are larger in size compared to controls

arrested B cell differentiation
- cells fail to progress efficiently from the immature stage to the transitional stage
- profound block in B cell development

decreased immunoglobulin level

increased pro-B cell number
- accumulate B220+CD43+ pro-B cells

abnormal B cell differentiation
- splenic B cells are larger in size and express higher membrane IgM levels indicating a defect in maturation to the B220^hiIgM^loIgD^hi stage

decreased B-1a cell number

decreased splenocyte number
- a 65% reduction in splenocyte numbers

decreased mature B cell number
- decrease in IgM+ peripheral B cells in the spleen and a marked reduction in B220^hiIgM+ and IgM^loIgD^hi B cells in the bone marrow and periphery, respectively
- older mice have increased numbers of B220+ IgM+ B cells compared to younger mice but the numbers are still more than 10 times lower than in age matched controls

absent B-1b cells
- absent from the spleen and peritoneum

mammalian phenotype

cardiovascular system phenotype
- Normal - despite the occurrence of hemorrhages in mice null for related proteins, no signs of gross hemorrhage are seen in these mice

References

Pappu R; Cheng AM; Li B; Gong Q; Chiu C; Griffin N; White M; Sleckman BP; Chan AC. 1999. Requirement for B cell linker protein (BLNK) in B cell development. Science 286(5446):1949-54PubMed: 10583957 MGI: J:58805

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Blnk
- Genotyping resources and troubleshooting
Breeding Considerations

The resulting chimeric animals were crossed to C57BL/6 mice for 10 generations. Specific pathogen-free (SPF) conditions are recommended.
- Additional Breeding and Husbandry Support
Citation
When using the BLNK KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004524 in your Materials and Methods section.

Overview

Also Known As:BLNK KO

Donating Investigator

Genetic overview

Blnktm1Achn

Research Applications

Details

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Genetics

Blnktm1Achn

Allele Symbol: Blnktm1Achn

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Blnktm1Achn related

Mammalian Phenotype Terms by Genotype

Genotype: Blnktm1Achn/Blnk+involves: 129S4/SvJae * 129X1/SvJ * BALB/c * C3H * C57BL/6

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Blnktm1Achn/Blnktm1Achninvolves: 129X1/SvJ

immune system phenotype

hematopoietic system phenotype

mammalian phenotype

References

Technical Support

Genotyping Protocols

Breeding Considerations

Citation

Related Strains

Blnk^tm1Achn

Blnk^tm1Achn

Allele Symbol: Blnk^tm1Achn

Genotype: Blnk^tm1Achn related

Genotype: Blnk^tm1Achn/Blnk⁺
involves: 129S4/SvJae * 129X1/SvJ * BALB/c * C3H * C57BL/6

Genotype: Blnk^tm1Achn/Blnk^tm1Achn
involves: 129X1/SvJ