These mice carry a mutant allele of Stat3 (signal transducer and activator of transcription 3) that has mutations in exon 23 which disrupt an internal splice acceptor thereby preventing production of the beta isoform. Homozygotes are more susceptible to bacterial endotoxicity. This mutant mouse strain may be useful in studies of inflammatory response and septic (endotoxin) shock.
Stephen V. Desiderio, Johns Hopkins Medical Institute
These mice carry a mutant allele that has mutations in exon 23 (YIIITG) which disrupt an internal splice acceptor thereby preventing production of the beta isoform. These mice express only the alpha isoform. No beta isoform protein is detected in hepatic tissue or MEFs from homozygotes by RT-PCR. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygotes are more susceptible to bacterial endotoxicity. Mutant mice are less likely to recover from LPS challenge than wildtype mice. This mutant mouse strain may be useful in studies of inflammatory response and septic (endotoxin) shock.
A targeting vector containing a loxP site flanked PGK-neo cassette was used to insert nucleotide substitutions in the polypyrimidine tract and AG dinucleotide of exon 23 (YIIITG), disrupting an internal splice acceptor and preventing production of the Stat3-beta isoform. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into C57BL/6 blastocysts. The resulting animals were backcrossed to 129X1/SvJ for 10 generations.
|Allele Name||targeted mutation 1, Stephen Desiderio|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Stat3, signal transducer and activator of transcription 3|
|Strain of Origin||129X1/SvJ|
|Molecular Note||Exon 23 was replaced with modified sequence in which nucleotide susbtitutions within 3 polypyrimidine tracts and an AG dinucleotide were made in order to disrupt an internal splice acceptor site specific to the beta isoform. Transcript encoding the beta isoform was undetected by RT-PCR analysis of homozygous mutant hepatic mRNA, while wild-type levels of transcript encoding the alpha isoform were observed. Analysis of MEFs reiterated these findings at the protein level.|
|Mutations Made By|| |
Stephen Desiderio, Johns Hopkins Medical Institute
When maintaining a live colony, these mice can be bred as homozygotes.
When using the 129X1-Stat3tm1Desi/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008862 in your Materials and Methods section.