B6.129S(Cg)-Stat1^tm1Dlv/J

Stock number: 012606
Product name: Stat1^-
Research areas: Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The Stat1- allele has a neo cassette replacing exons 3-5 and part of exon 2 of the signal transducer and activator of transcription 1 gene (Stat1) - abolishing endogenous gene function. These mice may be useful for studying the mechanisms of IFN-induced and STAT1-dependant resistance to infection.

Homozygous (Stat1^-/-) mice are viable and fertile when maintained under specific pathogen-free (SPF) conditions. In conventional health status vivaria (non-SPF), homozygotes tend to be runted and die within 48 hours of weaning due to hepatic necrosis due to viral infection.

Detailed description

The Stat1- allele has a neo cassette replacing exons 3-5 and part of exon 2 of the signal transducer and activator of transcription 1 gene (Stat1) - abolishing endogenous gene function. Homozygous (Stat1^-/-) mice are viable and fertile when maintained under specific pathogen-free (SPF) conditions. In conventional health status vivaria (non-SPF), homozygotes tend to be runted and die within 48 hours of weaning due to hepatic necrosis due to viral infection.

Stat1^-/- mice fail to mount transcriptional responses to IFNα or IFNγ, as shown by lack of induction of normal IFN inducible genes ISG54, IRF-1, or ISGF3γp48. STAT1 response results in abnormal innate immunity, but may be redundant in pathways other than IFN due to various compensatory mechanisms. These mice may be useful for studying the mechanisms of INF-induced and STAT1-dependant resistance to infection.

Development

A targeting vector was designed by Dr. David E. Levy (New York University School of Medicine) to replace exons 3-5 and part of exon 2 encoding the signal transducer and activator of transcription 1 (Stat1) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S/SvEv-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females and subsequently to CD1 mice to generate a colony of Stat1^-/- mice. These mice were backcrossed 8 generations to C57BL/6 background and following micro satellite marker analysis 100% C57BL/6 animals were selected for subsequent interbreeding. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Stat1^tm1Dlv
Name: targeted mutation 1, David E Levy
MGI accession ID: MGI:1930947
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Stat1
Marker name: signal transducer and activator of transcription 1
Chromosome: 1
Strain of origin: 129S/SvEv-Gpi1^c
Molecular note: A neomycin resistance cassette replaced 5.7 kb of sequence, including 3 exons and a portion of a fourth encoding amino acids 221-365. This allele produces a partial nonfunctional protein product.