B6.129S7-Slc7a2^tm1Clm/LellJ

Stock number: 022767
Product name: Cat2^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

In this strain, a neo cassette replaces replace 1.9 kb, including exon 2, of the solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 (Slc7a2) gene, abolishing gene expression. These mice may be useful for studying the control of CAT2 over inflammation and disease progression.

Detailed description

In this strain, a neo cassette replaces replace 1.9 kb, including exon 2, of the solute carrier family 7 (cationic amino acid transporter, y⁺ system), member 2 (Slc7a2) gene, abolishing membrane bound CAT2 activity. Mice homozygous for this Cat2^-/- allele are viable and fertile. CAT2 is a membrane associated protein involved in the cellular uptake of cationic amino acids such as arginine, lysine and ornithine. CAT2 plays a regulatory role in the activation of macrophages. Arginine is a substrate for nitric oxide synthase (NOS) during the production of nitric oxide (NO). The release of NO by inflammatory cells contributes to the progression of diseases such as cancer, arthritis, inflammatory bowel disease, Crohn's disease, and atherosclerosis. CAT2 plays a role in controlling inflammation and IL-17 activation in an injury model of colitis. These Cat2^-/- mice exhibit a reduction in NO biosynthesis in macrophages. They have increased numbers of memory T cells and activated dendritic cells in their lungs. When infected with Helicobacter pylori these mice display suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor. They exhibit altered cytokine expression.

Development

A targeting vector was designed to replace 1.9 kb, including exon 2, of the solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 (Slc7a2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.2 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, and these mice were bred together to generate a colony of Cat2^-/- mice. These mice were backcrossed for at least 10 generations to C57BL/6J background. 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

Symbol: Slc7a2^tm1Clm
Name: targeted mutation 1, Carol L MacLeod
MGI accession ID: MGI:2150359
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Slc7a2
Marker name: solute carrier family 7 (cationic amino acid transporter, y+ system), member 2
Chromosome: 8
Strain of origin: 129S7/SvEvBrd-Hprt^b-m2
Molecular note: A neomycin resistance cassette replaced 1.9 kb of sequence, including exon 2.