Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator David Milstone,   Brigham and Women's Hospital

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), 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.

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 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.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Sele^tm1Dmil allele

008238	129S-Seletm1Dmil/J
008236	B6.129S4-Seletm1Dmil/J

View Strains carrying   Sele^tm1Dmil     (2 strains)

Strains carrying other alleles of Sele

008238	129S-Seletm1Dmil/J
008439	B6.129S2-Seletm1Hyn Selltm1Hyn Selptm1Hyn/J
008437	B6.129S2-Seletm1Hyn Selptm1Hyn/J
008434	B6.129S2-Seletm2Hyn/J
008236	B6.129S4-Seletm1Dmil/J
003807	B6;129S-Seletm1Hyn Selltm1Hyn Selptm1Hyn/J
003806	B6;129S-Seletm2Hyn Selltm4Hyn/J
002916	B6;129S2-Seletm1Hyn Selptm1Hyn/J
002915	B6;129S2-Seletm2Hyn/J
008440	C.129S2(B6)-Seletm1Hyn Selltm1Hyn Selptm1Hyn/J
008438	C.129S2(B6)-Seletm1Hyn Selptm1Hyn/J
008435	C.129S2(B6)-Seletm2Hyn/J

View Strains carrying other alleles of Sele     (12 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Sele^tm1Dmil/Sele^tm1Dmil

        involves: 129S4/SvJae * C57BL/6J

• immune system phenotype
• abnormal leukocyte adhesion
  • TNFa treatment to stimulate an inflammatory response resulted in a significantly lower amount of adhesion in mutants vs wild-type   (MGI Ref ID J:113169)
  • numbers of adherent cells in wild-type prior to treatment is 74 adherent cells/sq. mm and in mutants 83 cells/sq. mm.; after TNF treatment, in wild-type there are 1745 adherent cells/sq. mm while in mutants there are 798 cells/sq. mm   (MGI Ref ID J:113169)
  • in mutants, fewer dermal microvessels support high adhesion densities compared to wild-type mice; a similar trend is observed in mesenteric microvessels   (MGI Ref ID J:113169)
• cellular phenotype
• abnormal leukocyte adhesion
  • TNFa treatment to stimulate an inflammatory response resulted in a significantly lower amount of adhesion in mutants vs wild-type   (MGI Ref ID J:113169)
  • numbers of adherent cells in wild-type prior to treatment is 74 adherent cells/sq. mm and in mutants 83 cells/sq. mm.; after TNF treatment, in wild-type there are 1745 adherent cells/sq. mm while in mutants there are 798 cells/sq. mm   (MGI Ref ID J:113169)
  • in mutants, fewer dermal microvessels support high adhesion densities compared to wild-type mice; a similar trend is observed in mesenteric microvessels   (MGI Ref ID J:113169)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Defects in Cell Adhesion Molecules

Cardiovascular Research
Vascular Defects
      defective leukocyte function

Cell Biology Research
Defects in Cell Adhesion Molecules

Developmental Biology Research
Defects in Cell Adhesion Molecules

Immunology and Inflammation Research
Inflammation
Lymphoid Tissue Defects

Internal/Organ Research
Lymphoid Tissue Defects

Research Tools
Cancer Research
Cardiovascular Research
Cell Biology Research
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Seletm1Dmil
Allele Name		targeted mutation 1, David Milstone
Allele Type		Targeted (knock-out)
Common Name(s)		E-selectin-; E-;
Mutation Made By		David Milstone,   Brigham and Women's Hospital
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Sele, selectin, endothelial cell
Chromosome		1
Gene Common Name(s)		CD62E; E-selectin; ELAM; ELAM1; ESEL; Elam; LECAM2; endothelial adhesion molecule;
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. [MGI Ref ID J:113169]

Genotyping

Genotyping Information

Genotyping Protocols

Sele^tm1Dmil, Melt Curve Analysis
Sele^tm1Dmil, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Milstone DS; Fukumura D; Padgett RC; O'Donnell PE; Davis VM; Benavidez OJ; Monsky WL; Melder RJ; Jain RK; Gimbrone MA Jr. 1998. Mice lacking E-selectin show normal numbers of rolling leukocytes but reduced leukocyte stable arrest on cytokine-activated microvascular endothelium. Microcirculation 5(2-3):153-71. [PubMed: 9789256]  [MGI Ref ID J:113169]

Additional References

Sele^tm1Dmil related

Bae SJ; Shimizu K; Yozaki M; Yamaoka T; Akiyama Y; Yoshizaki A; Muroi E; Hara T; Ogawa F; Sato S. 2010. Involvement of L-selectin in contact hypersensitivity responses augmented by auditory stress. Am J Pathol 176(1):187-97. [PubMed: 19948832]  [MGI Ref ID J:156378]

Gerritsen ME; Shen CP; Atkinson WJ; Padgett RC; Gimbrone MA Jr; Milstone DS. 1996. Microvascular endothelial cells from E-selectin-deficient mice form tubes in vitro. Lab Invest 75(2):175-84. [PubMed: 8765318]  [MGI Ref ID J:34956]

Hiratsuka S; Goel S; Kamoun WS; Maru Y; Fukumura D; Duda DG; Jain RK. 2011. Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A 108(9):3725-30. [PubMed: 21321210]  [MGI Ref ID J:170481]

Milstone DS; Redline RW; O'Donnell PE; Davis VM; Stavrakis G. 2000. E-selectin expression and function in a unique placental trophoblast population at the fetal-maternal interface: regulation by a trophoblast-restricted transcriptional mechanism conserved between humans and mice. Dev Dyn 219(1):63-76. [PubMed: 10974672]  [MGI Ref ID J:64541]

Yu Y; Moulton KS; Khan MK; Vineberg S; Boye E; Davis VM; O'Donnell PE; Bischoff J; Milstone DS. 2004. E-selectin is required for the antiangiogenic activity of endostatin. Proc Natl Acad Sci U S A 101(21):8005-10. [PubMed: 15148373]  [MGI Ref ID J:90657]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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.

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