Homozygous Ptpn22 (or pep) knockout mice exhibit increased numbers of activated effector/memory T cells, increased cytokine production, spontaneous germinal centers in the spleen and Peyer’s patches, elevated serum antibody levels, splenomegaly and lymphadenopathy. This strain may be useful for studying negative regulation in TCR signaling as well as stepwise requirement for the development of autoimmunity in mice.
Andrew C Chan, Genentech
The Ptpn22 (or pep) gene encodes the protein tyrosine phosphatase, non-receptor type 22 (lymphoid) protein that functions in the regulation of T cell receptor (TCR) signaling during T cell development and differentiation and is expressed in hematopoietic cells.
The Pep knockout allele has a puromycin cassette in exon 1 (E1).
While naive T cell activation in homozygous mice shows comparative growth to that of wild-type controls, TCR re-stimulation of these effector cells displays increased proliferation and cytokine production. In addition, mice spontaneously develop germinal centers in the spleen and Peyer’s patches as well as increased serum levels of IgG1, IgG2a and IgE.
In older mice (greater than 6 months of age), T cells numbers are increased within the effector/memory T cell pool in both the CD4 and CD8 compartments. The increase in lymphocyte numbers in the spleen and lymph nodes results in splenomegaly and lymphadenopathy.
This strain may be useful for studying the negative regulation of TCR signaling as well as stepwise requirement for the development of autoimmunity in mice.
A targeting vector was designed by Dr. Andrew C. Chan (Genentech) to insert a puromycin cassette upstream of exon 1 as well as altering the translation initiation methionine within exon 1 of the protein tyrosine phosphatase, non-receptor type 22 (lymphoid) gene (Ptpn22) on chromosome 3. The construct was electroporated into unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6 females to establish the colony. The resulting pep- (E1) mice were bred with C57BL/6 wildtype mice for at least 12 generations prior to sending males to The Jackson Laboratory Repository in 2016. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 2, Andrew C Chan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||pep-; pep(E1)-|
|Gene Symbol and Name||Ptpn22, protein tyrosine phosphatase, non-receptor type 22 (lymphoid)|
|Strain of Origin||Not Specified|
|Molecular Note||The translation initiation methionine in exon 1 was mutated from ATGG to CTGC and a puromycin resistance cassette added via homologous recombination. Immunoblot analysis confirmed the absence of wild type or truncated protein in thymocytes and splenocytes from homozygotes.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the pep- mouse strain in a publication, please cite the originating article(s) and include JAX stock #028977 in your Materials and Methods section.
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