B6.129P2-Blk^tm1Tara/J

Stock number: 017624
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Blk (B lymphoid kinase) knockout mice show no overt immune system defect. However, when combined with other redundant Src-family gene mutations, a role in NF-κB activation and B cell development can be seen.

Detailed description

Blk (B lymphoid kinase) is a Src-family protein tyrosine kinase specifically associated with B cells. Expression is eliminated in this knockout allele, as determined by Northern and Western blots of splenic B cells from homozygous mice. Although it is typically expressed during B cell development (in bone marrow) and is present in mature cells at high levels, there is no overt immune system defect in these animals. Development of B and T cells is unaltered. Both in vitro and in vivo B cell responses appear unchanged. Humoral immune responses of B cells to both T cell-dependent and -independent antigens are normal. Homozygotes are viable and fertile.

When combined with both Fyn (e.g. Stock No. 012468) and Lyn knockout mutations (sharing some redundant functionality), a role for the Blk gene in NF-κB activation during B cell development becomes apparent.

Development

A neomycin cassette inserted in reverse transcriptional orientation replaces portions of intron 7 and exon 8. The mutation was created in E14-1.1 129P2/OlaHsd-derived embryonic stem (ES) cells. The strain was backcrossed to C57BL/6 for 8 generations by the donating laboratory.

Allele

Symbol: Blk^tm1Tara
Name: targeted mutation 1, Alexander Tarakhovsky
MGI accession ID: MGI:2386868
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: blk^-
Marker symbol: Blk
Marker name: B lymphoid kinase
Marker synonyms: MODY11
Chromosome: 14
Strain of origin: 129P2/OlaHsd
Molecular note: Sequences encoding the essential portion of the kinase domain in exon 8 were replaced with a neomycin resistance gene via homologous recombination. Gene expression was not detected in splenic B-cells from homozygous mutant animals via Northern blot, but RT-PCR analysis detected transcripts containing exons 1-4. However, Western blot using antibodies directed against the N-terminal region of the protein did not detect any translation product from the truncated transcript.
General note: ES cell line = E14-1.1