These E-selectin mutant mice may be useful in studying inflammation, leukocyte rolling, leukocyte-endothelial adhesion, angiogenesis, and cancer.
David S Milstone, Brigham and Women's Hospital
Mice homozygous for this E-selectin mutant allele (E-/-) are viable and fertile with normal circulating leukocyte and platelet profiles. While several transcripts are generated from the mutant locus (due to transcription from the endogenous promoter and/or bidirectional transcription initiated from the pgk promoter in the neo-resistance cassette), these frame-shifted transcripts are non-functional with several predicted stop codons. In contrast to wildtype mice, no protein product is detected in several tissues isolated from LPS-injected homozygous mice. Homozygous mice exhibit abnormal responses to inflammatory stimuli. E-selectin deficiency results in endostatin unresponsiveness (as shown in corneal angiogenesis (mixed B6;129 genetic background) and aortic explant (C57BL/6 congenic background) experiments). These E-selectin mutant mice may be useful in studying inflammation, leukocyte rolling, leukocyte-endothelial adhesion, angiogenesis, and cancer.
Of note, E-selectin mutant mice are also be available on a C57BL/6J congenic background (Stock No. 008236), on a 129S congenic background (Stock No. 008238), on a mixed genetic background (Stock No. 002915), and along with other selectin mutations (Stock No. 002916, Stock No. 003806, and Stock No. 003807).
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. It should be noted that the phenotype of these E-selectin mutant mice could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exons 1-3 of the targeted gene with a reverse-oriented PGK-neo cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred with BALB/cJ to generate mutant mice. Next, mutant mice were backcrossed to BALB/cJ inbred mice for 11 generations prior to arrival at The Jackson Laboratory. The Y chromosome may not have been fixed to the genetic background during the backcross.
|Allele Name||targeted mutation 1, David Milstone|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||E-; E-selectin-|
|Gene Symbol and Name||Sele, selectin, endothelial cell|
|Strain of Origin||129S4/SvJae|
|Molecular Note||The neomycin resistance gene was substituted in reverse transcriptional orientation for sequence spanning from exon 1 to exon 3. Northern blot confirmed absence of transcript in mutant kidney, lung and heart samples.|
|Mutations Made By|| |
David Milstone, Brigham and Women's Hospital
When maintaining a live colony, homozygous mice may be bred.
When using the C.129S4-Seletm1Dmil/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008237 in your Materials and Methods section.