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

Former Names B6;129S-Seletm1Hyn Selltm1Hyn/J    (Changed: 29-APR-09 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+2p   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
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.

Development
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.

Related Strains

Strains carrying   Sele^tm2Hyn allele

008434	B6.129S2-Seletm2Hyn/J
002915	B6;129S2-Seletm2Hyn/J
008435	C.129S2(B6)-Seletm2Hyn/J

View Strains carrying   Sele^tm2Hyn     (3 strains)

Strains carrying other alleles of Sele

008238	129S-Seletm1Dmil/J
008437	B6.129S2-Seletm1Hyn Selptm1Hyn/J
008236	B6.129S4-Seletm1Dmil/J
003807	B6;129S-Seletm1Hyn Selltm1Hyn Selptm1Hyn/J
002916	B6;129S2-Seletm1Hyn Selptm1Hyn/J
008438	C.129S2(B6)-Seletm1Hyn Selptm1Hyn/J
008237	C.129S4-Seletm1Dmil/J

View Strains carrying other alleles of Sele     (7 strains)

Strains carrying other alleles of Sell

008436	B6.129S2-Selltm2Hyn/J
008441	B6.129S2-Selltm3Hyn Selptm1Hyn/J
003807	B6;129S-Seletm1Hyn Selltm1Hyn Selptm1Hyn/J
003805	B6;129S-Selltm3Hyn Selptm1Hyn/J
002917	B6;129S2-Selltm2Hyn/J
008442	C.129S2(B6)-Selltm3Hyn Selptm1Hyn/J
003860	NOD.129P2(B6)-Selltm1Tft/1LtJ
004943	NOD.Cg-Selltm1Tft Itgb7tm1Cgn/LtJ

View Strains carrying other alleles of Sell     (8 strains)

Phenotype

Phenotype Information

Currently there is no phenotype information for this strain.

Genes & Alleles

Gene & Allele Information

Allele Symbol		Seletm2Hyn
Allele Name		targeted mutation 2, Richard O Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		E-selectin-;
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
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		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. [MGI Ref ID J:31626]
Allele Symbol		Selltm4Hyn
Allele Name		targeted mutation 4, Richard O Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		L-selectin-;
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Sell, selectin, lymphocyte
Chromosome		1
Gene Common Name(s)		AI528707; CD62L; L-selectin; LAM1; LECAM-1; LECAM1; LEU8; LNHR; LSEL; LYAM1; Lnhr; Ly-22; Ly-m22; Lyam-1; Lyam1; PLNHR; TQ1; expressed sequence AI528707; lymph node homing receptor; lymphocyte adhesion molecule 1; lymphocyte antigen 22; lymphocyte antigen m22;
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. [MGI Ref ID J:57973]

Genotyping

Genotyping Information

Genotyping Protocols

Sele^tm1Hyn, Standard PCR
Sell^tm1Hyn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Additional References

Sele^tm2Hyn related

Belanger SD; St-Pierre Y. 2005. Role of selectins in the triggering, growth, and dissemination of T-lymphoma cells: implication of L-selectin in the growth of thymic lymphoma. Blood 105(12):4800-6. [PubMed: 15705798]  [MGI Ref ID J:107461]

Eriksson EE. 2008. No detectable endothelial- or leukocyte-derived L-selectin ligand activity on the endothelium in inflamed cremaster muscle venules. J Leukoc Biol 84(1):93-103. [PubMed: 18381812]  [MGI Ref ID J:137752]

Frenette PS; Mayadas TN; Rayburn H; Hynes RO; Wagner DD. 1996. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 84(4):563-74. [PubMed: 8598043]  [MGI Ref ID J:31626]

Fujita T; Fujimoto M; Matsushita T; Shimada Y; Hasegawa M; Kuwano Y; Ogawa F; Takehara K; Sato S. 2007. Phase-Dependent Roles of E-Selectin during Chronic Contact Hypersensitivity Responses. Am J Pathol 170(5):1649-58. [PubMed: 17456770]  [MGI Ref ID J:121083]

Hidalgo A; Peired AJ; Wild MK; Vestweber D; Frenette PS. 2007. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44. Immunity 26(4):477-89. [PubMed: 17442598]  [MGI Ref ID J:123577]

Homeister JW; Zhang M; Frenette PS; Hynes RO; Wagner DD; Lowe JB; Marks RM. 1998. Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation. Blood 92(7):2345-52. [PubMed: 9746773]  [MGI Ref ID J:50212]

Horikawa M; Fujimoto M; Hasegawa M; Matsushita T; Hamaguchi Y; Kawasuji A; Matsushita Y; Fujita T; Ogawa F; Takehara K; Steeber DA; Sato S. 2006. E- and P-selectins synergistically inhibit bleomycin-induced pulmonary fibrosis. Am J Pathol 169(3):740-9. [PubMed: 16936251]  [MGI Ref ID J:112363]

Kaifi JT; Hall LR; Diaz C; Sypek J; Diaconu E; Lass JH; Pearlman E. 2000. Impaired eosinophil recruitment to the cornea in P-selectin-deficient mice in onchocerca volvulus keratitis (River blindness) Invest Ophthalmol Vis Sci 41(12):3856-61. [PubMed: 11053286]  [MGI Ref ID J:65551]

Komura K; Hasegawa M; Hamaguchi Y; Saito E; Kaburagi Y; Yanaba K; Kawara S; Takehara K; Seki M; Steeber DA; Tedder TF; Sato S. 2003. Ultraviolet light exposure suppresses contact hypersensitivity by abrogating endothelial intercellular adhesion molecule-1 up-regulation at the elicitation site. J Immunol 171(6):2855-62. [PubMed: 12960307]  [MGI Ref ID J:85377]

Robinson SD; Frenette PS; Rayburn H; Cummiskey M; Ullman-Cullere M; Wagner DD; Hynes RO. 1999. Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci U S A 96(20):11452-7. [PubMed: 10500197]  [MGI Ref ID J:57973]

Taverna D; Moher H; Crowley D; Borsig L; Varki A; Hynes RO. 2004. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proc Natl Acad Sci U S A 101(3):763-8. [PubMed: 14718670]  [MGI Ref ID J:88109]

Tomita H; Iwata Y; Ogawa F; Komura K; Shimizu K; Yoshizaki A; Hara T; Muroi E; Yanaba K; Bae S; Takenaka M; Hasegawa M; Fujimoto M; Sato S. 2009. P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand. J Invest Dermatol 129(8):2059-67. [PubMed: 19177138]  [MGI Ref ID J:152512]

Yanaba K; Kaburagi Y; Takehara K; Steeber DA; Tedder TF; Sato S. 2003. Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition. Am J Pathol 162(5):1463-73. [PubMed: 12707029]  [MGI Ref ID J:113592]

Sell^tm4Hyn related

Robinson SD; Frenette PS; Rayburn H; Cummiskey M; Ullman-Cullere M; Wagner DD; Hynes RO. 1999. Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci U S A 96(20):11452-7. [PubMed: 10500197]  [MGI Ref ID J:57973]

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

Colony Maintenance

Breeding & Husbandry	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.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

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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.

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