Strain Detail Sheet

Strain Name:
B6;129P2-Dektm1Siwe/Mmmh
Stock Number:
067991-MU
Citation ID:
RRID:MMRRC_067991-MU
Other Names:
DEK knockout mice

Strain Information

Gene Details

Dektm1Siwe
Name: DEK proto-oncogene; targeted mutation 1, Susanne I Wells
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 13
Alteration at locus: Knockout
Dek
Name: DEK proto-oncogene
Synonyms: DEK proto-oncogene (DNA binding), D13H6S231E, 1810019E15Rik
Type: Gene
Species: Mouse
Chromosome: 13
Alteration at locus: Knockout
NCBI: 110052
HGNC: HGNC:2768
Homologene: 2593
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Genetic Alterations
An IRES-LacZ-Neo cassette was used to interrupt exon 6 of the mouse Dek gene.
ES Cell Line
E14 derived from 129P2/OlaHsd

Strain Description

Phenotype
Constitutive Dek knockout mice are phenotypically normal and healthy, with normal lifespans, and they can reproduce. However, these animals show distinct differences in response to stress compared to controls. For instance, the knockout mice survive repeated doses of radiation better than controls, largely due to hematopoietic progenitor cells remaining quiescent instead of undergoing apoptosis. This response to hematopoietic stress is also evident in the poor repopulating capacity of hematopoietic stem cells during bone marrow transplant. When the knockout mice are subjected to chemical or genetic oncogenic drivers, the mice develop fewer and/or smaller and less aggressive solid tumors. Finally, Dek knockout mice experience reduced inflammation responses, including joint inflammation in arthritis models, due to impaired formation of neutrophil extracellular traps (NETs).
MeSH Terms
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Chromosomal Proteins, Non-Histone/genetics
  • Chromosomal Proteins, Non-Histone/physiology
  • DNA-Binding Proteins/physiology
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms/etiology
  • Oncogene Proteins/genetics
  • Oncogene Proteins/physiology
  • Oncogene Proteins, Viral/genetics
  • Papilloma/etiology
  • Papillomavirus E7 Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Repressor Proteins/genetics
  • Breast Neoplasms/metabolism
  • Breast Neoplasms/pathology
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone/metabolism
  • DNA-Binding Proteins/metabolism
  • Gene Expression Regulation, Neoplastic
  • Neoplasms, Experimental
  • Oncogene Proteins/metabolism
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Wnt Signaling Pathway
  • DNA-Binding Proteins/genetics
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism
  • Mice, Knockout
  • Transplantation, Heterologous
  • Transplantation, Homologous
  • Adult
  • Aptamers, Nucleotide/therapeutic use
  • Arthritis, Juvenile/immunology
  • Arthritis, Juvenile/therapy
  • Chemotactic Factors/antagonists & inhibitors
  • Chemotactic Factors/genetics
  • Chemotactic Factors/immunology
  • Chemotactic Factors/metabolism
  • Chromosomal Proteins, Non-Histone/antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone/immunology
  • DNA-Binding Proteins/antagonists & inhibitors
  • Disease Models, Animal
  • Extracellular Traps/immunology
  • Extracellular Traps/metabolism
  • Healthy Volunteers
  • Male
  • Neutrophils/immunology
  • Oncogene Proteins/antagonists & inhibitors
  • Oncogene Proteins/immunology
  • Poly-ADP-Ribose Binding Proteins/antagonists & inhibitors
  • Poly-ADP-Ribose Binding Proteins/genetics
  • Poly-ADP-Ribose Binding Proteins/immunology
  • Poly-ADP-Ribose Binding Proteins/metabolism
  • Primary Cell Culture
  • Synovial Fluid/chemistry
  • Synovial Fluid/cytology
  • Synovial Fluid/immunology
  • Zymosan/immunology
  • DNA Damage
  • DNA-Binding Proteins/deficiency
  • Hematopoiesis/physiology
  • Oncogene Proteins/deficiency
  • Poly-ADP-Ribose Binding Proteins/deficiency
  • Radiation Tolerance/physiology
Strain Development
A fragment containing the 5′ half of the Dek open reading frame was subcloned into pBluescript, along with an IRES-LacZ-Neo selectable marker exon 6. The linearized targeting vector was electroporated into E14 mouse ES cells derived from 129P2/OlaHsd. G418-resistant clones were isolated and homologous recombinants were identified by using Southern blot analysis. Subsequent microinjection into C57BL/6 blastocysts. All clones produced chimeric offspring, which gave germline transmission of the targeted allele. Dek−/− mice were healthy and bred normally.
Suggested Control Mice
DEK wild-type animals

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.

Research Applications

  • Cancer
  • Cell Biology
  • Hematology
  • Immunology and Inflammation
  • Neurobiology

Strain Origin

Donor
Gerard Grosveld, Ph.D., St. Jude Children's Research Hospital.
Lisa Privette Vinnedge, Ph.D., Cincinnati Children's Hospital.
Susanne Wells, Ph.D., Cincinnati Children's Hospital Medical Center (CCHMC).
Primary Reference

Wise-Draper TM, Mintz-Cole RA, Morris TA, Simpson DS, Wikenheiser-Brokamp KA, Currier MA, Cripe TP, Grosveld GC, Wells SI. Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo. Cancer Res. 2009 Mar 1;69(5):1792-9. doi: 10.1158/0008-5472.CAN-08-2304. Epub 2009 Feb 17. (Medline PMID: 19223548)

Privette Vinnedge LM, Benight NM, Wagh PK, Pease NA, Nashu MA, Serrano-Lopez J, Adams AK, Cancelas JA, Waltz SE, Wells SI. The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers. Oncogene. 2015 Apr 30;34(18):2325-36. doi: 10.1038/onc.2014.173. Epub 2014 Jun 23. (Medline PMID: 24954505)

Broxmeyer HE, Kappes F, Mor-Vaknin N, Legendre M, Kinzfogl J, Cooper S, Hangoc G, Markovitz DM. DEK regulates hematopoietic stem engraftment and progenitor cell proliferation. Stem Cells Dev. 2012 Jun 10;21(9):1449-54. doi: 10.1089/scd.2011.0451. Epub 2011 Oct 27. (Medline PMID: 21943234)

Mor-Vaknin N, Saha A, Legendre M, Carmona-Rivera C, Amin MA, Rabquer BJ, Gonzales-Hernandez MJ, Jorns J, Mohan S, Yalavarthi S, Pai DA, Angevine K, Almburg SJ, Knight JS, Adams BS, Koch AE, Fox DA, Engelke DR, Kaplan MJ, Markovitz DM. DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis. Nat Commun. 2017 Feb 6;8:14252. doi: 10.1038/ncomms14252. (Medline PMID: 28165452)

Serrano-Lopez J, Nattamai K, Pease NA, Shephard MS, Wellendorf AM, Sertorio M, Smith EA, Geiger H, Wells SI, Cancelas JA, Privette Vinnedge LM. Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors. Exp Hematol. 2018 Mar;59:40-50.e3. doi: 10.1016/j.exphem.2017.12.009. Epub 2017 Dec 27. (Medline PMID: 29288703)

Pease NA, Shephard MS, Sertorio M, Waltz SE, Vinnedge LMP. DEK Expression in Breast Cancer Cells Leads to the Alternative Activation of Tumor Associated Macrophages. Cancers (Basel). 2020 Jul 17;12(7):1936. doi: 10.3390/cancers12071936. (Medline PMID: 32708944)

Colony and Husbandry Information

Special Considerations

Due to the likely role of DEK in DNA damage repair, the donor recommends using heterozygous mice for breeding to generate sibling pairs of wild-type (control) and homozygous knockout animals to limit the potential for additional mutations developing in the genetic background.

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Appearance

Coat Color
Black
Eye
Black

Breeding

MMRRC Breeding System
Random intra-strain mating
Generation
N/A
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 7 to 9 months 7 to 9 months
Bred to Homozygosity
No
Average litter size
4 to 6
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Esther Allay.

Conditions of Distribution

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Esther Allay

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
067991-MU-EMBRYO Cryo-preserved embryos $1,038.00 / $2,621.00
Non-Profit / For-Profit		 Aliquot Approximate quantity2 : 20-40 embryos / aliquot
067991-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit		 Aliquot Approximate quantity3
067991-MU-RESUS Litter recovered from cryo-archive $2,624.00 / $5,340.00
Non-Profit / For-Profit		 Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.