Homozygotes develop normally, have a normal life span, and are poor breeders. Pups often need fostering. Rectal prolapse of a non-infectious origin develops in 9% of homozygotes and/or extensive non-healing ulcerations occur at the eyelids and around the face. Small, focal fibrin deposits are occasionally seen in the intestines and in the sinusoids of the liver, and excessive fibrin deposits are seen in ulcerated skin or prolapsed rectum. Pulmonary clot lysis is comparable to that seen in normal wildtype siblings. Endotoxin induced venous thrombosis is increased over normal wildtype siblings. Fibrin dissolution by PLAU-deficient macrophages is greatly reduced but macrophage invasion into the peritoneal cavity after thioglycollate injection is unaffected. Homozygous knockout mice have increased levels of Abeta42 and Abeta40 in plasma. Brain Abeta levels are not significantly different than controls.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
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 all but 23 amino acids of the coding sequence. Targeting was done in 129S2/SvPas-derived D3 ES cells.
|Allele Name||targeted mutation 1, Richard C Mulligan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||UPA-; u-PA-|
|Gene Symbol and Name||Plau, plasminogen activator, urokinase|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The gene was disrupted using neomycin resistance cassette. The vector replaced genomic sequences encompassing all but 23 amino acids of the coding sequence. Targeting was confirmed by the absence of gene specific mRNA and immunoreactivity.|
|Mutations Made By|| |
Dr. Peter Carmeliet, University of Leuven
Homozygotes are poor breeders and pups often need fostering. Expected coat color from breeding:Black
When using the uPA- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002509 in your Materials and Methods section.