Ly108-/- mice may be useful for studying the role of Ly108 in the function and maturity of thymic lymphocytes.
Pamela L Schwartzberg, National Human Genome Research Institute, National Institutes of Health (NHGRI, NIH)
Ly108-/- mice have a STOP codon inserted into exon 2, and a neo cassette replaces exon 3 and part of exon 2, of the SLAM family member 6 (Slamf6) gene, abolishing gene expression. SLAMF6, also known as LY108, is a type I transmembrane protein expressed on Natural killer (NK), T and B lymphocytes, monocytes and dendritic cells. SLAMF6 associates with the adapter molecule SAP to modulate immune cell function and maturation. Engagement of Ly108 amplifies the TCR signaling in thymocytes, leading to the induction of transcription factors such as early growth response gene-2 (Egr-2) and the promyelocytic zinc finger transcription factor (PLZF), which is required for the development of activated phenotypes of innate T lymphocyte and of natural killer T (NKT) cells. These mice lack Slamf6 expression and exhibit a decrease in numbers of PLZF+ CD4+ T cells and a 40-50% reduction of thymic NKT cells. Mice homozygous for this allele are viable and fertile. Of note, C57BL/6 mice express multiple forms of Ly108, including the unique lupus-resistant C57BL/6 isoform of Ly108, Ly108-H1. Expression of all forms of SLAMF6 should be abolished in this strain.
A targeting vector was designed to insert a STOP codon in exon 2 and to replace exon 3 and part of exon 2 of the SLAM family member 6 (Slamf6) gene with a neomycin resistance (neo) cassette. The construct was electroporated into C57BL/6J-derived HGTC-8 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6J females. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Pamela L Schwartzberg|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Slamf6, SLAM family member 6|
|Strain of Origin||C57BL/6J|
|General Note||ES cell line = HGTC-8 (C57BL/6J)|
|Molecular Note||A stop codon was introduced into exon 2 and replaced part of exons 2 and 3 with a neo cassette. Flow cytometry confirmed the absence of protein expression.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Ly108- mouse strain in a publication, please cite the originating article(s) and include JAX stock #024669 in your Materials and Methods section.