129S-Sele^tm1Dmil/J

Stock number: 008238
Strain synonyms: 129SvEv congenic E-selectin
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These E-selectin mutant mice may be useful in studying inflammation, leukocyte rolling, leukocyte-endothelial adhesion, angiogenesis, and cancer.

Detailed description

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), a BALB/cJ congenic background (Stock No. 008237), 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.

Development

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 males were bred with C57BL/6J to generate mutant mice. Next, mutant mice were backcrossed to 129S6/SvEvTac 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

Symbol: Sele^tm1Dmil
Name: targeted mutation 1, David Milstone
MGI accession ID: MGI:3665314
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sele
Marker name: selectin, endothelial cell
Chromosome: 1
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.