These double knock-out mice exhibit a diminished response in neutrophil recruitment to the peritoneum in response to thioglycollate.
Dr. Richard Hynes, Massachusetts Institute of Technology
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Sele | selectin, endothelial cell |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Sell | selectin, lymphocyte |
Mice that are homozygous null for the Sele and Sell genes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Sele or Sell gene products (mRNA or protein) are detected. A slightly diminished response in neutrophil recruitment to the peritoneum in response to thioglycollate is observed, as is a diminished ability to interact with the venular endothelium resulting in increased "rolling" along the vessel wall. These mice are suitable for use in research applications studying leukocyte homeostasis, infectious diseases and inflammation.
Sequential mutation by homologous recombination was utilized to replace the Sele and Sell genes with drug-resistance genes for hygromycin and puromycin (respectively) in 129S2/SvPas-derived D3 embryonic stem (ES) cells. This approach was necessary because the Sele and Sell genes are too closely linked for double-deficient animals to be generated by mating single-deficient animals. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric offspring obtained.
Allele Name | targeted mutation 2, Richard Hynes |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | E-selectin- |
Gene Symbol and Name | Sele, selectin, endothelial cell |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 1 |
Molecular Note | A modified D3 ES cell line heterozygous for the Selptm1Hyn allele was targeted a second time. The exons encoding the signal peptide, lectin domain, and a portion of the epidermal growth factor domain were replaced by the insertion of a PGK-hygro cassette. Both Northern and RT-PCR analysis revealed an absence of normal mRNA for E-selectin but the presence of mRNA for P-selectin in extracts from cardiac and pulmonary tissue of homozygous mutant mice. This targeted mutation occurred in trans with the Selptm1Hyn mutation and were subsequently bred apart. |
Allele Name | targeted mutation 4, Richard Hynes |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | L-selectin- |
Gene Symbol and Name | Sell, selectin, lymphocyte |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 1 |
Molecular Note | The three selectin genes, Sele, Sell, and Selp, are found within a 300 kb genomic region. To generate double knockouts, ES cells heterozygote for the Selptm1Hyn and Seletm2Hyn null alleles in trans to each other were targeted a third time. A PGK-puro cassette was used to delete a 2.1 kb region containing the exons encoding the lectin domain and most of the epidermal growth factor domain. Flow cytometric analysis of homozygote leukocytes showed an absence of the L-selectin and E-selectin protein while P-selectin express was unaffected. Thus, this targeted mutation occurred in cis with the Seletm2Hyn allele and in trans with the Selptm1Hyn allele. Due to their genomic proximity, the Selltm3Hyn and Seletm2Hyn alleles should propagate together through the offspring. |
This strain originated on a B6;129S2 background and is maintained as a homozygote. The donating lab maintained these mice by avoiding brother-sister matings.
When using the EL- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003806 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Sele<tm1Hyn>, Homozygous for Sell<tm1Hyn> |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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