Strain Name:

B6.129S(Cg)-Ddit3tm2.1Dron/J

Stock Number:

005530

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Availability:

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Mice that are homozygous for the targeted mutation have mouse embryonic fibroblasts and renal proximal tubular epithelial cells with decreased apoptosis in response to endoplasmic reticulum stress induced by the toxin, tunicamycin. This mutant mouse strain may be useful in studies of apoptosis and pathogenesis due to endoplasmic reticulum stress.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
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Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Specieslaboratory mouse
GenerationN5+N2F2 (10-JAN-11)
Generation Definitions
 
Donating Investigator David Ron,   NYU School of Medicine

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (MRNA or protein) is detected by Northern or Western blot analysis of toxin challenged mouse embryonic fibroblasts (MEFs). MEFs and renal proximal tubular epithelial cells have decreased apoptosis in response to endoplasmic reticulum stress induced by the toxin, tunicamycin. Pancreatic islets cells are more resistant to nitric oxide induced apoptosis. MEFs exhibit a delayed onset of unfolded protein response (UPR) target gene expression when treated with tunicamycin. This mutant mouse strain may be useful in studies of apoptosis and pathogenesis due to endoplasmic reticulum stress. The Donating Investigator reports that lacZ activity is not detected.

Development
A targeting construct containing a NLS-lacZ cassette and a floxed PGK-Neo cassette was used to disrupt almost all the coding region in exons 3 and 4. The construct was electroporated into 129S6/SvEvTac derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The floxed selection cassette was later removed by Cre recombinase excision by crossing the mice to a Cre deleter strain. The donating investigator stated that the resulting mice were then crossed to C57BL/6 mice (see SNP note below) for 5 generations.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 26 of 27 markers throughout the genome suggested a C57BL/6 genetic background (1 segregating for 129 on Chromosome 1), at least 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   See control note: C57BL/6J mice (Stock No. 000664) may be used as controls.
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Myxoid Liposarcoma   (DDIT3)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ddit3tm1Dron/Ddit3tm1Dron

        B6.129-Ddit3tm1Dron
  • immune system phenotype
  • abnormal macrophage activation involved in immune response
    • macrophages treated with excess lipoprotein-cholesterol or tunicamycin fail to exhibit an increase in IP3-induced calcium release unlike similarly wild-type   (MGI Ref ID J:153833)
  • decreased macrophage apoptosis
    • under cholesterol loading conditions, macrophages treated exhibit less apoptosis compared with similarly treated wild-type macrophages   (MGI Ref ID J:153833)
  • cellular phenotype
  • decreased macrophage apoptosis
    • under cholesterol loading conditions, macrophages treated exhibit less apoptosis compared with similarly treated wild-type macrophages   (MGI Ref ID J:153833)
  • hematopoietic system phenotype
  • abnormal macrophage activation involved in immune response
    • macrophages treated with excess lipoprotein-cholesterol or tunicamycin fail to exhibit an increase in IP3-induced calcium release unlike similarly wild-type   (MGI Ref ID J:153833)
  • decreased macrophage apoptosis
    • under cholesterol loading conditions, macrophages treated exhibit less apoptosis compared with similarly treated wild-type macrophages   (MGI Ref ID J:153833)

The following phenotype relates to a compound genotype created using this strain.
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Ddit3tm1Dron/Ddit3tm1Dron

        either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)
  • cellular phenotype
  • decreased apoptosis
    • MEFs prepared from E13.5 embryos exhibit less programmed cell death when challenged with agents that perturb ER function   (MGI Ref ID J:52729)
    • homozygotes treated with tunicamycin to induce ER stress and renal insufficiency exhibit decreased programmed cell death in the renal proximal tubular epithelium   (MGI Ref ID J:52729)
  • homeostasis/metabolism phenotype
  • abnormal response to injury
    • homozygotes treated with tunicamycin to induce ER stress and renal insufficiency exhibit decreased programmed cell death in the renal proximal tubular epithelium compared to controls despite impaired renal function   (MGI Ref ID J:52729)

Ddit3tm1Dron/Ddit3tm1Dron

        involves: 129S1/Sv * 129X1/SvJ * FVB/N
  • immune system phenotype
  • decreased susceptibility to viral infection
    • homozygotes infected with a neurovirulent virus, Moloney MLV-ts1, exhibit a small, but significant, delay of about 4.5 days in the incubation period of the disease that correlates with a decrease in early virus replication   (MGI Ref ID J:112354)

Ddit3tm1Dron/Ddit3tm1Dron

        involves: 129S1/Sv * 129X1/SvJ
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype
    • homozygotes have a normal pancreas   (MGI Ref ID J:129974)
View Research Applications

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

Apoptosis Research
Endogenous Regulators
Extracellular Modulators

Cell Biology Research
DNA Damage Response

Research Tools
Apoptosis Research
Toxicology Research
      free radical research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ddit3tm2.1Dron
Allele Name targeted mutation 2.1, David Ron
Allele Type Targeted (Null/Knockout, Reporter)
Common Name(s) CHOP::LacZ;
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Ddit3, DNA-damage inducible transcript 3
Chromosome 10
Gene Common Name(s) C/EBP homoologous protein 10; CEBPZ; CHOP; CHOP-10; CHOP10; GADD153;
Molecular Note A NLS-lacZ cassette and a floxed PGK-Neo cassette replaced the coding region in parts of exons 3 and 4. Cre-emdiated recombination removed the neo cassette. [MGI Ref ID J:101977]

Genotyping

Genotyping Information

Genotyping Protocols

Ddit3tm1Dron, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Genetic Resource Science at The Jackson Laboratory. 2008. Expression/Specificity patterns of Cre transgenes MGI Direct Data Submission :.  [MGI Ref ID J:137887]

Additional References

Ddit3tm2.1Dron related

Carlisle RE; Brimble E; Werner KE; Cruz GL; Ask K; Ingram AJ; Dickhout JG. 2014. 4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression. PLoS One 9(1):e84663. [PubMed: 24416259]  [MGI Ref ID J:212207]

Chen CM; Wu CT; Chiang CK; Liao BW; Liu SH. 2012. C/EBP homologous protein (CHOP) deficiency aggravates hippocampal cell apoptosis and impairs memory performance. PLoS One 7(7):e40801. [PubMed: 22815824]  [MGI Ref ID J:189613]

Deslauriers AM; Afkhami-Goli A; Paul AM; Bhat RK; Acharjee S; Ellestad KK; Noorbakhsh F; Michalak M; Power C. 2011. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J Immunol 187(9):4788-99. [PubMed: 21964030]  [MGI Ref ID J:179506]

Ferlito M; Wang Q; Fulton WB; Colombani PM; Marchionni L; Fox-Talbot K; Paolocci N; Steenbergen C. 2014. Hydrogen sulfide [corrected] increases survival during sepsis: protective effect of CHOP inhibition. J Immunol 192(4):1806-14. [PubMed: 24403532]  [MGI Ref ID J:209401]

Lozon TI; Eastman AJ; Matute-Bello G; Chen P; Hallstrand TS; Altemeier WA. 2011. PKR-dependent CHOP induction limits hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 300(3):L422-9. [PubMed: 21186267]  [MGI Ref ID J:171168]

Moisoi N; Klupsch K; Fedele V; East P; Sharma S; Renton A; Plun-Favreau H; Edwards RE; Teismann P; Esposti MD; Morrison AD; Wood NW; Downward J; Martins LM. 2009. Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response. Cell Death Differ 16(3):449-64. [PubMed: 19023330]  [MGI Ref ID J:158086]

Mueller K; Sunami Y; Stuetzle M; Guldiken N; Kucukoglu O; Mueller S; Kulaksiz H; Schwarz P; Strnad P. 2013. CHOP-mediated hepcidin suppression modulates hepatic iron load. J Pathol :. [PubMed: 23749468]  [MGI Ref ID J:202871]

Murakami T; Ockinger J; Yu J; Byles V; McColl A; Hofer AM; Horng T. 2012. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A 109(28):11282-7. [PubMed: 22733741]  [MGI Ref ID J:186406]

Nashine S; Bhootada Y; Lewin AS; Gorbatyuk M. 2013. Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration. PLoS One 8(4):e63205. [PubMed: 23646198]  [MGI Ref ID J:200547]

Pfaffenbach KT; Gentile CL; Nivala AM; Wang D; Wei Y; Pagliassotti MJ. 2010. Linking endoplasmic reticulum stress to cell death in hepatocytes: roles of C/EBP homologous protein and chemical chaperones in palmitate-mediated cell death. Am J Physiol Endocrinol Metab 298(5):E1027-35. [PubMed: 20159858]  [MGI Ref ID J:162886]

Posey KL; Coustry F; Veerisetty AC; Liu P; Alcorn JL; Hecht JT. 2012. Chop (Ddit3) Is Essential for D469del-COMP Retention and Cell Death in Chondrocytes in an Inducible Transgenic Mouse Model of Pseudoachondroplasia. Am J Pathol 180(2):727-37. [PubMed: 22154935]  [MGI Ref ID J:180513]

Scaiewicz V; Nahmias A; Chung RT; Mueller T; Tirosh B; Shibolet O. 2013. CCAAT/enhancer-binding protein homologous (CHOP) protein promotes carcinogenesis in the DEN-induced hepatocellular carcinoma model. PLoS One 8(12):e81065. [PubMed: 24339898]  [MGI Ref ID J:211163]

Shenderov K; Riteau N; Yip R; Mayer-Barber KD; Oland S; Hieny S; Fitzgerald P; Oberst A; Dillon CP; Green DR; Cerundolo V; Sher A. 2014. Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1beta in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway. J Immunol 192(5):2029-33. [PubMed: 24489101]  [MGI Ref ID J:209937]

The Jackson Laboratory. 2005. Information obtained from The Jackson Laboratory, Bar Harbor, ME Unpublished :.  [MGI Ref ID J:101977]

Wu J; Ruas JL; Estall JL; Rasbach KA; Choi JH; Ye L; Bostrom P; Tyra HM; Crawford RW; Campbell KP; Rutkowski DT; Kaufman RJ; Spiegelman BM. 2011. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1alpha/ATF6alpha complex. Cell Metab 13(2):160-9. [PubMed: 21284983]  [MGI Ref ID J:169564]

Zhang Y; Larade K; Jiang ZG; Ito S; Wang W; Zhu H; Bunn HF. 2010. The flavoheme reductase Ncb5or protects cells against endoplasmic reticulum stress-induced lipotoxicity. J Lipid Res 51(1):53-62. [PubMed: 19609006]  [MGI Ref ID J:157053]

Zhao L; Rosales C; Seburn K; Ron D; Ackerman SL. 2010. Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome. Hum Mol Genet 19(1):25-35. [PubMed: 19801575]  [MGI Ref ID J:154993]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating SystemHomozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Ddit3tm2.1Dron  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Ddit3tm2.1Dron x Homozygous for Ddit3tm2.1Dron  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Ddit3tm2.1Dron  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Ddit3tm2.1Dron x Homozygous for Ddit3tm2.1Dron  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   See control note: C57BL/6J mice (Stock No. 000664) may be used as controls.
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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