B6.129S6(FVB)-Fastk^tm1.1Andp/J

Stock number: 017295
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These FAST^-/- knock out mice are less sensitive to induced pulmonary inflammation and may be useful in studies of mRNA stability, stress granules, immune response and FAS-mediated apoptosis.

Detailed description

In a house dust mite antigen-induced pulmonary inflammation model, the number of inflammatory cells in bronchoalveolar lavage (BAL) fluids from homozygotes was similar to that seen in wildtype controls, however there were virtually no neutrophils in the BAL fluids from homozygous mice. Homozygotes are less sensitive to LPS induced pulmonary inflammation with reduced vascular leakage of protein in BAL fluid. Neutrophil chemotaxis, survival and phagocytic activity are not defective. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of MEFs from homozygotes.

Development

A targeting vector containing a floxed NEO cassette was used to disrupt 4.3 kb of sequence, the entire coding sequence, of the gene. The construct was electroporated into 129S6/SvEvTac derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to C57BL/6J females. The mice were then crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (STOCK No. 3724) mice to remove the floxed NEO selection cassette. The mice were then backcrossed to C57BL/6J for 14 generations, and no longer contain the cre transgene. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Fastk^tm1.1Andp
Name: targeted mutation 1, Paul Anderson
MGI accession ID: MGI:4461026
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fastk
Marker name: Fas-activated serine/threonine kinase
Chromosome: 5
Strain of origin: 129S6/SvEvTac
Molecular note: The coding sequence was replaced by a floxed neo cassette. The selection cassette was removed by cre mediated recombination.