B6.129S2-Serpine1^tm1Mlg/J

Stock number: 002507
Product name: PAI-1^-
Research areas: Cancer Research, Internal/Organ Research

Description

These plasminogen activator inhibitor-1 deficient mice may be useful for studying the role of fibrosis and fibrinolysis in amyloid plaque deposition (Alzheimer's disease), hyperphagia, obesity, injury and muscular dystrophy.

Detailed description

Mice homozygous for this plasminogen activator inhibitor-1 null allele (PAI-1-) are viable and fertile with normal development. Compared to wildtype mice, pulmonary clot lysis is increased in the heterozygote and further increased in the homozygote. Endotoxin induced venous thrombosis is decreased compared to wildtype mice. Thus, disruption of the PAI-1 (Serpine1) gene induces a mild hyperfibrinolytic state. Hemostasis is normal in homozygous mutants.

Development

The plasminogen activator inhibitor-1 (PAI-1 or Serpine1) targeted null mutation was made in the laboratories of Dr. Richard Mulligan (Whitehead Institute for Biomedical Sciences) and of Dr. Peter Carmellet (University of Leuven). A targeting vector was used which resulted in the neomycin-resistant gene replacing all coding sequences. The Serpine1 gene was isolated from a BALB/c genomic library and targeting was done in D3 ES cells.

Allele

Symbol: Serpine1^tm1Mlg
Name: targeted mutation 1, Richard C Mulligan
MGI accession ID: MGI:1857287
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Serpine1
Marker name: serine (or cysteine) peptidase inhibitor, clade E, member 1
Chromosome: 5
Strain of origin: 129S2/SvPas
Molecular note: A PGK-neomycin resistance cassette replaced all of the Serpine1 coding sequence and part of the promoter region including the transcription initiation site. Northern blot analysis did not detect Serpine1 mRNA in endotoxin-treated homozygous mutant liver. Neither untreated nor endotoxin-treated homozygous mutant kidney produced detectable SERPINE1 immunoreactivity. A monoclonal antibody based immunofunctional assay did not detect protein levels in plasma of endotoxin-treated homozygous mutant mice.