These Lcp2 knockout mice exhibit a complete loss of T cells and γδ-TCR+ lymphocytes, but maintain a normal number of B cells, macrophages, neutrophils, mast cells and NK cells. They may be useful for studies related to T cell development.
Gary Koretzky, University of Pennsylvania
SLP-76 is an immune cell adaptor expressed in T lymphocytes, macrophages, mast cells, platelets, neutrophils, and natural killer (NK) cells. It has been shown to play a role in lymphatic vascular development, T cell receptor (TCR) signaling, as well as signaling through receptors that use tyrosine base activation motifs in platelet, mast cells, neutrophils and NK cells. In these lymphocyte cytosolic protein 2 (Lcp2) knockout mice, a neomycin resistance cassette in reverse orientation disrupts the gene and abolishes Lcp2 expression. These mice have small lymph nodes and enlarged spleens when compared to controls. They exhibit a complete loss of T cells and γδ-TCR+ lymphocytes, but maintain a normal number of B cells, macrophages, neutrophils, mast cells and NK cells. Some homozygotes may be viable, but are born at a frequency lower than typical Mendelian ratios would predict. Substantial perinatal lethality is observed.
A targeting vector was designed to replace 360 bp including exon 1 and the translational start site of the lymphocyte cytosolic protein 2 (Lcp2) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reports that these mice were backcrossed for at least 10 generations to C57BL/6J mice (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 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 1, Gary A Koretzky|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lcp2, lymphocyte cytosolic protein 2|
|Gene Synonym(s)||AI323664; BB161688; SLP-76; SLP76; Slp76; expressed sequence AI323664; expressed sequence BB161688; t-wimp; twm; twm|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||Approximately 360 bp of the gene, including part of exon 1 and the translation initiation site, was replaced with a neo cassette via homologous recombination. RT-PCR analysis of homozygous mutant animals verified the absence of gene expression. Western blot and immunohistochemistry of spleen from homozygous mutant animals did not detect protein product.|
|Mutations Made By|| |
Gary Koretzky, University of Pennsylvania
When maintaining a live colony, heterozygous mice may be bred together. The donating investigator reports that homozygotes are viable but born at a frequency lower than Mendelian, with substantial perinatal lethality.
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