Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation ?+N1F9 (04-DEC-07)   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.

Development
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 recipient blastocysts. The floxed selection cassette was later removed by Cre recombinase excision by crossing the mice to a Cre deleter strain. The animals were then crossed to C57BL/6 mice for 5 generations.

Control Information

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

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Ddit3^tm1Dron/Ddit3^tm1Dron

        either: (involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)

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

Ddit3^tm1Dron/Ddit3^tm1Dron

        involves: 129S1/Sv * 129X1/SvJ * FVB/N

• immune system phenotype
• decreased susceptibility to viral infection (MGI Ref ID J:112354)
  • 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

Ddit3^tm1Dron/Ddit3^tm1Dron

        involves: 129S1/Sv * 129X1/SvJ

• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:129974)
  • homozygotes have a normal pancreas

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

Allele Symbol		Ddit3tm1Dron
Allele Name		targeted mutation 1, David Ron
Allele Type		Targeted (knock-out)
Common Name(s)		chop-;
Mutation Made By		Rivka Jungreis,
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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; MGC124604; MGC4154;
Molecular Note		A PGK-neomycin resistance cassette replaced the coding region in parts of exons 3 and 4. Northern blot analyses did not detect transcript in MEFs from homozygous mutant E13.5 embryos. [MGI Ref ID J:52729]

Genotyping

Genotyping Information

Genotyping Protocols

Ddit3^tm1Dron, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Marciniak SJ; Yun CY; Oyadomari S; Novoa I; Zhang Y; Jungreis R; Nagata K; Harding HP; Ron D. 2004. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev 18(24):3066-77. [PubMed: 15601821]  [MGI Ref ID J:95320]

Additional References

Ddit3^tm1Dron related

Clase AC; Dimcheff DE; Favara C; Dorward D; McAtee FJ; Parrie LE; Ron D; Portis JL. 2006. Oligodendrocytes are a major target of the toxicity of spongiogenic murine retroviruses. Am J Pathol 169(3):1026-38. [PubMed: 16936275]  [MGI Ref ID J:112354]

Iida K; Li Y; McGrath BC; Frank A; Cavener DR. 2007. PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice. BMC Cell Biol 8:38. [PubMed: 17727724]  [MGI Ref ID J:129974]

Pennuto M; Tinelli E; Malaguti M; Del Carro U; D'Antonio M; Ron D; Quattrini A; Feltri ML; Wrabetz L. 2008. Ablation of the UPR-mediator CHOP restores motor function and reduces demyelination in Charcot-Marie-Tooth 1B mice. Neuron 57(3):393-405. [PubMed: 18255032]  [MGI Ref ID J:135317]

Seimon TA; Obstfeld A; Moore KJ; Golenbock DT; Tabas I. 2006. Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages. Proc Natl Acad Sci U S A 103(52):19794-9. [PubMed: 17167049]  [MGI Ref ID J:118240]

Zinszner H; Kuroda M; Wang X; Batchvarova N; Lightfoot RT; Remotti H; Stevens JL; Ron D. 1998. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12(7):982-95. [PubMed: 9531536]  [MGI Ref ID J:52729]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
		C57BL/6J mice (Stock No. 000664) may be used as controls.
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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