B6.129P2-Vnn1^tm1Pna/RtrkJ

Stock number: 022802
Product name: Vanin-1 -
Strain synonyms: V1-, Val1 KO
Research areas: Apoptosis Research, Immunology, Inflammation and Autoimmunity Research, Metabolism Research

Description

These Val1 KO mice may be useful for studying immune responses to oxidative stress.

Detailed description

In this strain, a neo cassette replaces exon 1 of the Vanin 1 (Vnn) gene, abolishing gene expression. Vanin 1 is a GPI-anchored pantetheinase highly expressed in epithelial cells of the GI, liver, and kidney. Vanin 1 activity produces cysteamine, which decreases the protective activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) against reactive oxygen species (ROS) toxicity, inducing oxidative stress. Vanain 1 has also been associated with the migration of T-cell progenitors to the thymus. Mice homozygous for this allele are viable and fertile. These KO mice lack cysteamine production and exhibit resistance to oxidative injury, and reduced apoptosis and inflammation. They have decreased superoxide production, and show increased resistance to oxidative stress. PPARγ expression is suppressed.

Development

A targeting vector was designed to replace exon 1 of the Vanin 1 (Vnn) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and the resulting chimeric males were bred to C57BL/6 females. The donating investigator reported that these mice were bred to C57BL/6 mice for at least 9 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

In 2014, 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, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data show that the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background, and the living colony in 2105 is on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Vnn1^tm1Pna
Name: targeted mutation 1, Philippe Naquet
MGI accession ID: MGI:3027932
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Vnn1
Marker name: vanin 1
Chromosome: 10
Strain of origin: 129P2/OlaHsd
Molecular note: Exon 1 was replaced with a PGK neomycin cassette in reverse orientation. Northern blot analysis of mRNA from kidney and RT-PCR confirmed the absence of transcript while Western blot analysis and immunohistochemistry demonstrated the absence of protein.
General note: \