Overview

Also Known As:PL-

These double knock-out mice exhibit reductions in leukocyte rolling and in extravasation of neutrophils in thioglycollate-induced peritonitis.

Donating Investigator

Dr. Richard Hynes, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Sell^tm3Hyn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Sell	selectin, lymphocyte

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Selp	selectin, platelet

Research Applications

Immunology, Inflammation and Autoimmunity Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous null for the Sell and Selp genes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Sell and Selp gene products (mRNA or protein) are detected. Leukocytes from these mice exhibit a deficiency in the ability to interact with, and roll along, the venular wall endothelium. Such a deficiency in the crucial first step of leukocyte recruitment to surrounding tissues in response to infection or injury results in elevated leukocyte counts in the peripheral blood. These defects are largely due to absence of Selp. In addition, lack of Sell leads to failure of lymphocytes to enter lymph nodes and gthus to hypoplastic lymph nodes. These mice are suitable for use in research applications studying leukocyte homing, infectious diseases and inflammation.

Development

Sequential mutation by homologous recombination was utilized to replace the Sell and Selp genes with drug-resistance genes for neomycin and puromycin (respectively) in 129S2/SvPas derived D3 embryonic stem (ES) cells. This approach was necessary because the Sell and Selp 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.

Genetics

Sell^tm3Hyn

Allele Symbol: Sell^tm3Hyn

Allele Name	targeted mutation 3, 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 Selp^tm1Hyn and Sele^tm2Hyn 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 P-selectin protein while E-selectin expression was unaffected. Thus, this targeted mutation occurred in cis with the Selp^tm1Hyn allele and in trans with the Sele^tm2Hyn allele. Due to their genomic proximity, the Sell^tm3Hyn and Selp^tm1Hyn alleles should propagate together through the offspring.

Selp^tm1Hyn

Allele Symbol: Selp^tm1Hyn

Allele Name	targeted mutation 1, Richard Hynes
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	P-; P-selectin^-; P-Selp^-
Gene Symbol and Name	Selp, selectin, platelet
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	1
Molecular Note	A portion of exon 3 encoding 10 amino acids of a signal peptide and 27 amino acids of the lectin domain was replaced with a PGK-neo cassette. Mice were treated with lipopolysaccharide to augment the normally low levels of selectin in lung and liver tissue. A longer transcript, resulting from aberrant or cryptic splicing involving the neomycin cassette, was detected at low levels in mutant mice by Northern blot analysis. RT-PCR further confirmed the presence of low levels of transcript in homozygous mice. Immunofluorescence analysis of activated platelets and lung sections from homozygous mutant mice showed an absence of encoded protein. These results were further confirmed by flow cytometric analysis of activated platelets and metabolic labeling of lung tissue.
Mutations Made By	Dr. Richard Hynes, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Selp^tm1Hyn related

Immunology, Inflammation and Autoimmunity Research
- Inflammation
- CD Antigens, Antigen Receptors, and Histocompatibility Markers

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Sell^tm3Hyn/Sell^tm3Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas * C57BL/6

cellular phenotype

impaired leukocyte tethering or rolling
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF

immune system phenotype

impaired eosinophil recruitment
- 2-fold fewer eosinophils are recruited to the peritoneum in response to ragweed allergen challenge

impaired leukocyte tethering or rolling
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF

impaired neutrophil recruitment
- lower numbers of neutrophils are observed than those elicited from mice that are null homozygotes for just one gene
- neutrophil influx in thioglycollate-induced peritonitis is inhibited at 2, 4, and 8 hours after injection compared to wild-type mice
- numbers of neutrophils increased between 8- 24 hours post injection whereas in wild-type mice they decrease

increased eosinophil cell number
- eosinophil numbers are about 4-fold higher in the blood

increased leukocyte cell number
- leukocyte numbers are slightly increased

increased neutrophil cell number
- neutrophils numbers are slightly increased

hematopoietic system phenotype

impaired eosinophil recruitment
- 2-fold fewer eosinophils are recruited to the peritoneum in response to ragweed allergen challenge

impaired leukocyte tethering or rolling
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF

impaired neutrophil recruitment
- lower numbers of neutrophils are observed than those elicited from mice that are null homozygotes for just one gene
- neutrophil influx in thioglycollate-induced peritonitis is inhibited at 2, 4, and 8 hours after injection compared to wild-type mice
- numbers of neutrophils increased between 8- 24 hours post injection whereas in wild-type mice they decrease

increased eosinophil cell number
- eosinophil numbers are about 4-fold higher in the blood

increased leukocyte cell number
- leukocyte numbers are slightly increased

increased neutrophil cell number
- neutrophils numbers are slightly increased

References

Additional - Sell^tm3Hyn related

Additional - Selp^tm1Hyn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Selp
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the PL- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003805 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Selp<tm1Hyn>, Homozygous for Sell<tm1Hyn>, 1 pair minimum

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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General Terms and Conditions

Questions about Terms of Use

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Also Known As:PL-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selltm3Hyn

Allele Symbol: Selltm3Hyn

Selptm1Hyn

Allele Symbol: Selptm1Hyn

Disease Terms

Research Areas By Phenotype

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

Genotype: Selptm1Hyn related

Mammalian Phenotype Terms by Genotype

Genotype: Selltm3Hyn/Selltm3Hyn Selptm1Hyn/Selptm1Hyninvolves: 129S2/SvPas * C57BL/6

cellular phenotype

immune system phenotype

hematopoietic system phenotype

References

Additional - Selltm3Hyn related

Additional - Selptm1Hyn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Sell^tm3Hyn

Allele Symbol: Sell^tm3Hyn

Selp^tm1Hyn

Allele Symbol: Selp^tm1Hyn

Genotype: Selp^tm1Hyn related

Genotype: Sell^tm3Hyn/Sell^tm3Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas * C57BL/6

Additional - Sell^tm3Hyn related

Additional - Selp^tm1Hyn related