This WASP deficient mutant mouse strain on the congenic C57BL/6 background is mildly immunodeficient, exhibiting thrombocytopenia, lymphocytopenia, and defective secondary T-cell response to influenza virus. These mice may be useful in studies of autoimmunity and Wiskott-Aldrich syndrome.
Ted S. Strom, Memphis VAMC
Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency, is caused by mutation of the WAS gene that result in defective actin polymerization. These mice carry a knockout of the Was (Wiskott-Aldrich syndrome) gene in which a NEO cassette disrupts exon 7. Female mice that are homozygous for this allele and male mice that are hemizygous for this X linked allele are viable and fertile. No gene product (mRNA or protein) is detected by Northern blot analysis of B cell and T cells from homozygotes or Western blot analysis of thymocytes, B cell and T cells from homozygotes.
Mice carrying the Wastm1Sbs targeted mutation on a congenic C57BL/6J background are mildly immunodeficient, exhibiting thrombocytopenia, lymphocytopenia, and defective secondary T-cell response to influenza virus. Hemizygous males on the congenic C57BL/6J background do not develop the colitis phenotype observed in mutant mice on the 129 background. These mutant mice exhibit reduced platelet count, increased susceptibility to Streptococcus pneumoniae infection, and delayed clearance of Mycobacterium bovis. With age, these mutant mice produce autoantibodies and glomerulonephritis. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
A targeting vector generated by Dr. Scott Snapper, while at the Boston Children's Hospital and Harvard Medical School, containing a NEO cassette was used to disrupt exon 7, which encodes part of the protein GTPase-binding domain. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 or 129Sv female mice, and then backcrossed to C57BL/6J for 8 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony. The gene is X-linked.
|Allele Name||targeted mutation 1, Scott B Snapper|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Was-; wasp-|
|Gene Symbol and Name||Was, Wiskott-Aldrich syndrome|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A neomycin cassette was inserted into exon 7, which encodes part of the GTPase-binding domain. The absence of transcript and protein produced from the targeted allele in male hemizygous mutant mice was confirmed by Northern blot and Western blot analyses.|
|Mutations Made By|| |
Dr. Scott Snapper, Massachusetts General Hospital
When maintaining a live colony, these mice can be bred as female homozygotes and male hemizygotes. The gene is X-linked.
When using the wasp- mouse strain in a publication, please cite the originating article(s) and include JAX stock #019458 in your Materials and Methods section.