These Serpinb9-deficient (Spi6-/-) mutant mice have impaired cytotoxic T lymphocyte (CTL) immunity to viruses and may be useful in studies of viral immune response and inflammation, and the exocytosis pathway in CTL apoptosis.
Dr. Philip G. Ashton-Rickardt, Imperial College London
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by RT-PCR analysis of myeloid and lymphoid cells. After experimental viral infection, homozygous mice have lower (five to nine-fold reduction) numbers of virus specific cytotoxic T lymphocytes (CTLs) and increased apoptosis of virus specific CD8 T cells when compared to wildtype controls. Mutant mice have impaired Lymphocytic Choriomeningitis virus (LCMV) infection clearance. Granzyme A and granzyme B specific activity is reduced in cytotoxic granules and increased in CTL cytoplasm. Mutant CTLs have a three-fold increase in the number of granules lacking granzyme B. This mutant mouse strain may be useful in studies of viral immune response and inflammation, and the exocytosis pathway in CTL apoptosis.
A targeting vector containing a floxed neomycin resistance selection cassette was used to disrupt exon 7, which contains most of the coding sequence.
The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells (Ware et al. Transgenic Res. 12, 743.), which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into BALB/c blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for 20 generations.
|Allele Name||targeted mutation 1, Philip G Ashton-Rickardt|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||M Spi6 delta Neo; Spi6-|
|Gene Symbol and Name||Serpinb9, serine (or cysteine) peptidase inhibitor, clade B, member 9|
|Strain of Origin||C57BL/6|
|Molecular Note||Exon 7 was replaced with a floxed neomycin resistance cassette that was subsequently removed.|
|Mutations Made By|| |
Dr. Philip Ashton-Rickardt, Imperial College London
When maintaining a live colony, these mice can be bred as homozygotes.
When using the C57BL/6-Serpinb9tm1Arp/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008158 in your Materials and Methods section.