Description

Strain Information

Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-MAR-06 Species laboratory mouse Generation F?+13p+F2 (22-JAN-09) Generation Definitions   Donating Investigator Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)

Description
These DR-4 mice harbor three independently segregating loci that collectively express four drug resistance genes. The Dnmt1^tm3Jae targeted mutation on chromosome 9 confers resistance to both neomycin/G418 and puromycin (while retaining Dnmt1 function). The pPWL512hyg transgene (unknown genomic insertion) results in hygromycin resistance. These three resistance genes are controlled by the promoter and polyadenylation signal of the murine 3-phosphoglycerate kinase gene (Pgk1), which ensures high levels of expression in both embryonic stem (ES) cells and mouse embryonic fibroblasts (MEFs). The Hprt^b-m3 mutation on the X chromosome confers resistance to 6-thioguanine (and abolishes endogenous Hprt function).

MEFs prepared from DR-4 mice display resistance to concentrations of the drugs G418, puromycin, 6-thioguanine and hygromycin well above those used normally for the selection of drug-resistant ES cells. This mouse strain represents an economical donor for the production of multiple-drug resistant MEFs.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pgk1

002354	C57BL/6J-Tg(pPWL512hyg)1Ems/J
002355	C57BL/6J-Tg(pPWL88puro)2Ems/J

View Strains carrying other alleles of Pgk1     (2 strains)

Strains carrying other alleles of hyg

002354

C57BL/6J-Tg(pPWL512hyg)1Ems/J

View Strains carrying other alleles of hyg     (1 strain)

Strains carrying other alleles of neo

010633	B6(Cg)-Gt(ROSA)26Sortm1(CAG-taulacZ)Bene/J
012247	B6.129-Aldh1a1tm1Gdu/J
012838	B6.129S4-Tnfrsf4tm1Nik/J
006382	B6;129-Casktm1Sud/J
016857	B6;129-Itga7tm1Burk/J
010711	C57BL/6-Ptrh2tm1Eruo/J
002356	C57BL/6J-Tg(pPGKneobpA)3Ems/J
009063	STOCK Ednrbtm1Nrd/J
012940	STOCK Snta1tm1Scf/J

View Strains carrying other alleles of neo     (9 strains)

Strains carrying other alleles of puro

002355

C57BL/6J-Tg(pPWL88puro)2Ems/J

View Strains carrying other alleles of puro     (1 strain)

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Research Tools
General Purpose
      multiple-drug resistant mouse embryonic fibroblasts
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Production of Targeted Mutations (Knockouts)
      Mutagenesis and Transgenesis: Production of Targeted Mutations (Knockouts), feeder cells for ES cell lines
Reproductive Biology Research
      multiple drug resistant embryonic fibroblasts

neo related

Research Tools
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Production of Targeted Mutations (Knockouts), feeder cells for ES cell lines

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(DR4)1Jae
Allele Name		transgene insertion 1, Rudolf Jaenisch
Allele Type		Not Applicable
Common Name(s)		DR-4; DR4;
Mutation Made By		Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)
Strain of Origin		129P2/OlaHsd and 129S4/SvJae and BALB/c and C57BL/6
Expressed Gene		hyg, hygromycin resistance, bacteria
Expressed Gene		puro, puromycin resistance,
Expressed Gene		neo, neomycin resistance, bacterial
Promoter		Pgk1, phosphoglycerate kinase 1, rat
Gene Symbol and Name		Tg(DR4)1Jae, transgene insertion 1, Rudolf Jaenisch
Chromosome		UN
General Note		Mouse embryonic fibroblasts prepared from the DR4 mouse strain displayed resistance to concentrations of four drugs (G418, 6-thioguanine, puromycin, and hygromycin) well above those used normally for the selection of drug resistant ES cells.
Molecular Note		The symbol Tg(DR4)1Jae represents a combination of three mutations (two transgenes and a knock-in) that together confer resistance to four drugs in STOCK Tg(DR4)1Jae/J mice. The DR4 strain was produced by the intercross of three strains: one strain carries the knock-in Dnmt1tm3Jae, which contains neomycin and puromycin resistance genes; a second strain carries Tg(pPWL512hyg)1Ems, which contains the hygromycin resistance gene; and the third strain carries Tg(Hprt1)1Jae, which is a knock-in of Hprtb-m3 and confers 6-TG resistance (6-thioguanine). A series of matings incorporated all 4 drug resistance genes into the DR4 strain. The phosphoglycerate kinase 1 promoter controls expression of each drug resistance gene. [MGI Ref ID J:92995]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Puromycin-QPCR, Separated QPCR
Generic Hygromycin, QPCR
Tg(DR4)1Jae Dnmt, Melt Curve Analysis
Tg(DR4)1Jae Dnmt, Standard PCR
Tg(DR4)1Jae/J HPRT, Melt Curve Analysis
Tg(DR4)1Jae/J HPRT, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tucker KL; Wang Y; Dausman J; Jaenisch R. 1997. A transgenic mouse strain expressing four drug-selectable marker genes. Nucleic Acids Res 25(18):3745-6. [PubMed: 9278500]  [MGI Ref ID J:92995]

Additional References

Tucker KL; Beard C; Dausmann J; Jackson-Grusby L; Laird PW; Lei H; Li E; Jaenisch R. 1996. Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. Genes Dev 10(8):1008-20. [PubMed: 8608936]  [MGI Ref ID J:83179]

Tg(DR4)1Jae related

Hsiao FC; Lin M; Tai A; Chen G; Huber BT. 2006. Cutting edge: Epstein-Barr virus transactivates the HERV-K18 superantigen by docking to the human complement receptor 2 (CD21) on primary B cells. J Immunol 177(4):2056-60. [PubMed: 16887963]  [MGI Ref ID J:138376]

Johnson KA; Lerner CP; Di Lacio LC; Laird PW; Sharpe AH; Simpson EM. 1995. Transgenic mice for the preparation of hygromycin-resistant primary embryonic fibroblast feeder layers for embryonic stem cell selections. Nucleic Acids Res 23(7):1273-5. [PubMed: 7739908]  [MGI Ref ID J:92459]

Tucker KL; Beard C; Dausmann J; Jackson-Grusby L; Laird PW; Lei H; Li E; Jaenisch R. 1996. Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. Genes Dev 10(8):1008-20. [PubMed: 8608936]  [MGI Ref ID J:83179]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	These DR-4 mice harbor three independently segregating loci that collectively express four drug resistance genes. When maintaining a live colony, females homozygous for the Dnmt1tm3Jae allele, homozygous for the X-linked Hprtb-m3 allele, and homozygous for the pPWL512hyg transgene may be bred with males homozygous for the Dnmt1tm3Jae allele, hemizygous for the X-linked Hprtb-m3 allele, and homozygous for the pPWL512hyg transgene. The expected coat color is albino.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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