B6.129S2-Plat^tm1Mlg/J

Stock number: 002508
Product name: t-PA^-
Research areas: Hematological Research

Description

These plasminogen activator, tissue knock-out (Plat^tm1Mlg, also commonly referred to as tPA^-) mice may be useful in fibrosis, neurovascular and other studies involving the widespread physiological effects of plasminogen activator.

Detailed description

Homozygotes develop normally, are fertile and have a normal life span. There are no histological abnormalities. Pulmonary clot lysis is 21% that of normal wildtype siblings. Endotoxin induced venous thrombosis is increased over that seen in normal wildtype siblings. Fibrin dissolution by PLAT-deficient macrophages is unaffected.

Development

This targeted mutant was made in the laboratories of Dr. Richard Mulligan of the Whitehead Institute for Biomedical Sciences, Cambridge Massachusetts and of Dr. Peter Carmellet at the Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium. A targeting vector was used which resulted in the neomycin-resistant gene (neo) replacing genomic sequences encoding most of the kringle-2 domain and part of the proteinase domain, including the essential histidine-326 residue. Targeting was done in 129S2/SvPas derived D3 ES cells. The mice were backcrossed to C57BL/6 for 8 generations.

Allele

Symbol: Plat^tm1Mlg
Name: targeted mutation 1, Richard C Mulligan
MGI accession ID: MGI:1857288
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Plat
Marker name: plasminogen activator, tissue
Chromosome: 8
Strain of origin: 129S2/SvPas
Molecular note: The gene was disrupted using neomycin resistance cassette. The vector replaced genomic sequences encoding most of the kringle-2 domain and part of the proteinase domain, including the catalytically essential histidine residue at position 326. Targeting was confirmed by the absence of gene specific mRNA and immunoreactivity.