B6.129P2-Lcn2^tm1Aade/AkiJ

Stock number: 024630
Product name: Lcn2^-
Research areas: Immunology, Inflammation and Autoimmunity Research, Metabolism Research

Description

Lcn2 deficient mice may be useful for studying the role of iron trafficking in the regulation of innate immunity.

Detailed description

A neo cassette replaces exons 2-5 of the lipocalin 2 (Lcn2) gene, abolishing gene expression. LCN2 is an iron-trafficking protein involved in apoptosis and the regulation of the innate immune systems response to bacterial growth and infection. Toll-like receptors on innate immune cells stimulate the production and secretion of LCN2 upon bacterial infection. LCN2 limits bacterial growth by iron sequestration, which is required by bacteria in order to replicate.

Homozygous LCN2-deficient mice are viable and fertile and should be housed in a specific pathogen free (SPF) facility. Escherichia coli challenge causes an increase in bacterial burden in the liver and spleen along with physical signs of sepsis such as lethargy, hunched posture, and ruffled fur. E Coli infection caused no difference in leukocyte numbers, neutrophil infiltration, or tissue iron distribution. Also, after induction of accelerated nephrotoxic serum nephritis (NTS), LCN2 KO mice exhibit more glomerular damage with increased proteinuria and interstitial leukocyte accumulation than wildtype mice.

Other mutations of Lcn2 show this gene to be a bone-derived hormone with metabolic regulatory effects. In these mutants, LCN2 suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone intake.

Development

A targeting vector was designed to replace exons 2-5 of the lipocalin 2 (Lcn2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were backcrossed for at least 10 generations to C57BL/6J mice. 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: Lcn2^tm1Aade
Name: targeted mutation 1, Alan Aderem
MGI accession ID: MGI:3525578
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lcn2
Marker name: lipocalin 2
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: A neo replaced coding exons 2-5. Absence of transcript was demonstrated by Northern blot analysis of mutant peritoneal macrophages. Immunoblot of mutant cell lysates confirmed the lack of protein.