B6;129S6-Gadd45b^tm1Flv/J

Stock number: 013101
Research areas: Apoptosis Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This Gadd45b targeted mutation strain may be useful in studies of autoimmune disease.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Isolated T cells exhibit increased proliferation with activation. Th1 cells from homozygotes are more resistant to activation induced apoptosis. 10 month old homozygotes exhibit mild splenomegaly. Homozygotes are more susceptible to experimental autoimmune encephalomyelitis, with longer duration and severity: 60% of homozygotes die when challenged with a higher dose of heat-inactivated Mycobacterium tuberculosis, compared to no deaths in controls. Immunocomplex deposits develop in the glomeruli of homozygotes.

Development

A targeting vector containing a Neo cassette was used to disrupt exons 3 and 4. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony. In January 2011, 32 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed that this strain is segregating at 5 markers likely from a mix of B6 and 129.

Allele

Symbol: Gadd45b^tm1Flv
Name: targeted mutation 1, Richard A Flavell
MGI accession ID: MGI:2687355
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Gadd45b
Marker name: growth arrest and DNA-damage-inducible 45 beta
Chromosome: 10
Strain of origin: 129S6/SvEvTac
Molecular note: Exons 3 and 4 were replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded residues 42 through 161, which make up crucial domains of the protein.