B6.129-Hif1a^tm1Kats/J

Stock number: 024640
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Hif1a isoform I.1 knockout mice demonstrate an increased resistance to bacterial infection.

Detailed description

The Hif1a (hypoxia inducible factor 1, alpha subunit) gene plays an anti-inflammatory and tissue-protective role by negatively regulating T cell functions. T cell activation leads to up-regulation of the I.1 isoform which represents less than 30% of the total Hif1a mRNA.

This strain carries a targeted knockout of the I.1 isoform of Hif1a. Isoform I.2 is normally expressed. Unlike the total knockouts of the gene, isolated disruption of the I.1 isoform does not result in embryonic death. Deletion of the isoform is sufficient to markedly enhance TCR-triggered cytokine secretion. Isoform I.1 knockout mice have stronger resistance to bacterial infection. T lymphocytes and macrophages display augmented responses to pathogen. Data suggests the gene is also important for regulation of T cell responses in cancer.

Development

A 0.5 kb fragment encoding exon I.1 was replaced with a loxP-exon I.1-loxP-neo-loxP cassette through homologous recombination in 129-derived embryonic stem (ES) cells. Properly targeted clones were transfected with Cre recombinase to excise both the exon and neomycin cassette. Chimeric animals were generated. This strain was backcrossed to C57BL/6 for 10 generations by the donating laboratory.

Allele

Symbol: Hif1a^tm1Kats
Name: targeted mutation 1, Dorthe M Katschinski
MGI accession ID: MGI:3641209
Generation method: Targeted
Attributes: Modified isoform(s)
Marker symbol: Hif1a
Marker name: hypoxia inducible factor 1, alpha subunit
Chromosome: 12
Strain of origin: 129
Molecular note: A floxed neo cassette was inserted downstream of the testis specific exon I.1 and an additional loxP site was introduced upstream of exon I.1. by homologous recombination. Cre mediated recombination removed the neo cassette and exon I.1. Expression of the ubiqutous isoform using exon I.2 was intact.