Overview

Also Known As: B6-iDTR, ROSA26iDTR

The Cre-inducible expression of DTR in these iDTR mutant mice render cells susceptible to ablation following Diphtheria toxin administration.

Donating Investigator

Ari Waisman, Johannes Gutenberg University of Mainz

Genetic overview

Genetic Background	Generation
	N?+pN2F13 (2019-07-12 00:00:00)

Gt(ROSA)26Sor^{tm1(HBEGF)Awai}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)	Gt(ROSA)26Sor	gene trap ROSA 26, Philippe Soriano

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Research Applications

Neurobiology Research
Research Tools

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

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Details

Detailed Description

Mice homozygous for this iDTR mutation are viable and fertile. These mice have the simian Diphtheria Toxin Receptor (DTR; from simian Hbegf) inserted into the Gt(ROSA)26Sor (ROSA26) locus. Widespread expression of DTR is blocked by an upstream loxP-flanked STOP sequence. When bred to Cre recombinase-expressing mice, the STOP sequence is deleted in tissues where Cre is present, permitting DTR expression. Cells expressing DTR are rendered susceptible to ablation following Diphtheria toxin administration.

For example, when bred to a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 006785), this mutant mouse strain may be useful in studies of lymphocyte cell ablation.

When crossed to a strain expressing Cre recombinase in oocytes (see Stock No. 011062), this mutant mouse strain may be useful in studies of ovarian development.

When crossed to a strain expressing Cre recombinase in the pituitary and, at lower levels, in the testes (see Stock No. 011069), this mutant mouse strain may be useful in studies of metabolic dysfunction.

Of note, iDTR mice are also available on a BALB/cBy congenic background (as Stock No. 008040) and a NOD congenic background (as Stock No. 016603).

Of note, The Jackson Laboratory Repository also distributes RC::L-DTA mice (Stock No. 026944), which have Cre recombinase-dependent inverted tox176 attenuated diphtheria toxin subunit alpha gene (DTA*G128D), as well as widespread eGFP fluorescence in the absence of Cre recombinase.

Development

A targeting vector was designed with a loxP-flanked STOP cassette upstream of the open reading frame of the simian Diphtheria Toxin Receptor (DTR; from simian hbEGF cDNA (base pair 56-682)). The loxP-flanked region contains two SV40 polyA signals, an frt-flanked neomycin resistance gene, and a transcriptional STOP cassette. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation of C57BL/6-derived Bruce4 ES embryonic stem (ES) cells. Correctly targeted ES cells were microinjected in CB20 blastocysts. Chimeric mice were bred to C57BL/6 to generate heterozygous "iDTR" mice. The donating investigator reported that these iDTR mice were maintained as homozygotes on the C57BL/6 genetic background (see SNP note below) prior to arrival at The Jackson Laboratory.

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 27 markers throughout the genome suggested a C57BL/6 genetic background, 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.

Expression Data

Expressed Gene	DTR, Simian Diphtheria Toxin Receptor,
Expressed Gene	HBEGF, heparin binding EGF like growth factor, chimpanzee
Site of Expression

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Buch T; Heppner FL; Tertilt C; Heinen TJ; Kremer M; Wunderlich FT; Jung S; Waisman A. 2005. A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods 2(6):419-26PubMed: 15908920 MGI: J:131076

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Genetics

Gt(ROSA)26Sor^{tm1(HBEGF)Awai}

Allele Symbol: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}

Allele Name	targeted mutation 1, Ari Waisman
Allele Type	Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence)
Allele Synonym(s)	targeted mutation 1, Ari Waisman; Gt(ROSA)26Sor^{tm1(HBEGF)Awai}
Gene Symbol and Name	Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano
Gene Synonym(s)	beta geo; ROSA26; R26; Gtrgeo26; Gtrosa26; Gtrgeo26; Gtrosa26; AV258896; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; SETD5-AS1; Thumpd3as1
Expressed Gene	DTR, Simian Diphtheria Toxin Receptor,
Expressed Gene	HBEGF, heparin binding EGF like growth factor, chimpanzee
Strain of Origin	B6.Cg-Thy1^a
Chromosome	6
Molecular Note	A targeting vector was designed with a loxP-flanked STOP cassette upstream of the open reading frame of the simian Diphtheria Toxin Receptor (DTR; from simian hbEGF cDNA (base pair 56-682)). The loxP-flanked region contains two SV40 polyA signals, an frt-flanked neomycin resistance gene, and a transcriptional STOP cassette. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation of C57BL/6-derived Bruce4 ES embryonic stem (ES) cells. Widespread expression of DTR is blocked by an upstream loxP-flanked STOP sequence. When bred to Cre recombinase-expressing mice, the STOP sequence is deleted in tissues where Cre is present, permitting DTR expression. Cells expressing DTR are rendered susceptible to ablation following Diphtheria toxin administration.
Mutations Made By	Ari Waisman, Johannes Gutenberg University of Mainz

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

isolated growth hormone deficiency

Research Areas By Genotype

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

Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
  - Mutagenesis and Transgenesis
- Diabetes and Obesity Research
  - loxP
- Reproductive Biology Research
  - Cre-lox System
- Cell Biology Research
- Cardiovascular Research
  - Cre-lox System
- Developmental Biology Research
  - Cre-lox System

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Cd19^tm1(cre)Cgn/? Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor^{tm1(HBEGF)Awai}
involves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

abnormal B cell morphology
- CD19-expressing B cells are absent after intraperitoneal injection of diptheria toxin for 7 days

abnormal bone marrow cell number
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

abnormal lymphocyte cell number
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

abnormal lymphocyte morphology
- after 3 or 7 days of diptheria toxin treatment, splenic B to T lymphocyte ratio decreases from 2.1 in controls to 0.6 and 0.3 respectively in double transgenic mice

abnormal splenic cell ratio
- with diptheria toxin treatment 3 times daily for 7 days, B cells are virtually absent from the spleen

absent immature B cells
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

absent mature B cells
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

immune system phenotype

abnormal B cell morphology
- CD19-expressing B cells are absent after intraperitoneal injection of diptheria toxin for 7 days

abnormal lymph node cell ratio
- with diptheria toxin treatment 3 times daily for 7 days, B cells are virtually absent from the lymph nodes

abnormal lymphocyte cell number
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

abnormal lymphocyte morphology
- after 3 or 7 days of diptheria toxin treatment, splenic B to T lymphocyte ratio decreases from 2.1 in controls to 0.6 and 0.3 respectively in double transgenic mice

abnormal splenic cell ratio
- with diptheria toxin treatment 3 times daily for 7 days, B cells are virtually absent from the spleen

absent immature B cells
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

absent mature B cells
- in bone marrow, drastic reductions in numbers of immature and mature B cells is observed

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor^{tm1(HBEGF)Awai} Tg(Gdf9-icre)5092Coo/0
involves: C57BL/6

cellular phenotype

oocyte degeneration
- oocytes have undergone apoptosis in preantral follicles

endocrine/exocrine gland phenotype

abnormal granulosa cell morphology
- cells have undergone apoptosis in preantral follicles

abnormal ovarian follicle morphology
- with diptheria toxin administration to 8-week-old pregnant females, oocytes and granulosa cells in preantral oocytes show apoptosis 9 days later, in contrast to treated controls where atretic follicles but not preantral follicles show apoptosis

abnormal ovary morphology

reproductive system phenotype

abnormal granulosa cell morphology
- cells have undergone apoptosis in preantral follicles

abnormal ovarian follicle morphology
- with diptheria toxin administration to 8-week-old pregnant females, oocytes and granulosa cells in preantral oocytes show apoptosis 9 days later, in contrast to treated controls where atretic follicles but not preantral follicles show apoptosis

abnormal ovary morphology

oocyte degeneration
- oocytes have undergone apoptosis in preantral follicles

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor⁺ Tg(Gh1-cre)bKnmn/0
involves: C57BL/6 * FVB/N

adipose tissue phenotype

increased retroperitoneal fat pad weight
- in diphtheria toxin-treated mice

increased subcutaneous adipose tissue amount
- in diphtheria toxin-treated mice

increased total body fat amount
- in diphtheria toxin-treated mice fed standard chow or a high fat diet

integument phenotype

increased subcutaneous adipose tissue amount
- in diphtheria toxin-treated mice

liver/biliary system phenotype

decreased liver triglyceride level
- in diphtheria toxin-treated mice fed a high-fat

decreased liver weight
- in diphtheria toxin-treated mice fed standard chow or a high fat diet

nervous system phenotype

decreased somatotroph cell number
- in diphtheria toxin-treated mice

small adenohypophysis
- in diphtheria toxin-treated mice

behavior/neurological phenotype

decreased fluid intake
- in diphtheria toxin-treated mice fed a low-fat

endocrine/exocrine gland phenotype

decreased somatotroph cell number
- in diphtheria toxin-treated mice

small adenohypophysis
- in diphtheria toxin-treated mice

growth/size/body region phenotype

decreased body weight
- in diphtheria toxin-treated mice fed a high fat diet

decreased lean body mass
- in diphtheria toxin-treated mice

homeostasis/metabolism phenotype

abnormal circulating hormone level

abnormal energy expenditure

abnormal gas homeostasis

abnormal glucose homeostasis

decreased circulating glucose level
- in diphtheria toxin-treated mice when fed a high-fat diet or a low-fat diet during an insulin tolerance test
- in diphtheria toxin-treated mice when fed standard chow

decreased circulating growth hormone level
- in diphtheria toxin-treated mice fed a high-fat or low-fat diet

decreased circulating insulin level
- in diphtheria toxin-treated mice when a high-fat diet or a low-fat diet

decreased circulating insulin-like growth factor I level
- in diphtheria toxin-treated mice fed a high-fat or low-fat diet

decreased energy expenditure
- in diphtheria toxin-treated mice fed a low-fat during the nocturnal phase or when mice are fed a high-fat diet

decreased liver triglyceride level
- in diphtheria toxin-treated mice fed a high-fat

decreased oxygen consumption
- in diphtheria toxin-treated mice fed a low-fat during the nocturnal phase

impaired glucose tolerance
- in diphtheria toxin-treated mice fed a high-fat

increased circulating leptin level
- in diphtheria toxin-treated mice

increased insulin sensitivity
- in diphtheria toxin-treated mice when fed standard chow, a high-fat diet, or a low-fat diet

increased respiratory quotient
- in diphtheria toxin-treated mice fed a low-fat

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor⁺ Tg(Krt1-15-cre/PGR)22Cot/0
involves: C57BL/6J * SJL/J

cellular phenotype

increased cell proliferation
- mice treated with RU486 prior to diphtheria toxin injection exhibit reduced proliferation and atrophy in the esophageal epithelia compared with wild-type mice

digestive/alimentary phenotype

abnormal esophageal epithelium morphology
- mice treated with RU486 prior to diphtheria toxin injection exhibit reduced proliferation and atrophy in the esophageal epithelia compared with wild-type mice

References

Buch T; Heppner FL; Tertilt C; Heinen TJ; Kremer M; Wunderlich FT; Jung S; Waisman A. 2005. A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods 2(6):419-26PubMed: 15908920 MGI: J:131076

Additional References

Zhu P; Wu J; Wang Y; Zhu X; Lu T; Liu B; He L; Ye B; Wang S; Meng S; Fan D; Wang J; Yang L; Qin X; Du Y; Li C; He L; Ren W; Wu X; Tian Y; Fan Z. 2018. LncGata6 maintains stemness of intestinal stem cells and promotes intestinal tumorigenesis. Nat Cell Biol 20(10):1134-1144PubMed: 30224759 MGI: J:268724
Chen Y; Ikeda K; Yoneshiro T; Scaramozza A; Tajima K; Wang Q; Kim K; Shinoda K; Sponton CH; Brown Z; Brack A; Kajimura S. 2019. Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature 565(7738):180-185PubMed: 30568302 MGI: J:269371
Kreisel T; Wolf B; Keshet E; Licht T. 2019. Unique role for dentate gyrus microglia in neuroblast survival and in VEGF-induced activation. Glia 67(4):594-618PubMed: 30453385 MGI: J:271655

Additional - Gt(ROSA)26Sor^{tm1(HBEGF)Awai} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Probe: Gt(rosa)26sor^Tm1Sor Probe
- Standard PCR: Gt(ROSA)26Sor^tm1sor STD
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the ROSA26iDTR mouse strain in a publication, please cite the originating article(s) and include JAX stock #007900 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available Now

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Gt(ROSA)26Sor<tm1(HBEGF)Awai>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Also Known As: B6-iDTR, ROSA26iDTR

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Gt(ROSA)26Sortm1(HBEGF)Awai

Allele Symbol: Gt(ROSA)26Sortm1(HBEGF)Awai

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cd19tm1(cre)Cgn/? Gt(ROSA)26Sortm1(HBEGF)Awai/Gt(ROSA)26Sortm1(HBEGF)Awaiinvolves: 129P2/OlaHsd * C57BL/6

hematopoietic system phenotype

immune system phenotype

Genotype: Gt(ROSA)26Sortm1(HBEGF)Awai/Gt(ROSA)26Sortm1(HBEGF)Awai Tg(Gdf9-icre)5092Coo/0involves: C57BL/6

cellular phenotype

endocrine/exocrine gland phenotype

reproductive system phenotype

Genotype: Gt(ROSA)26Sortm1(HBEGF)Awai/Gt(ROSA)26Sor+ Tg(Gh1-cre)bKnmn/0involves: C57BL/6 * FVB/N

adipose tissue phenotype

integument phenotype

liver/biliary system phenotype

nervous system phenotype

behavior/neurological phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Gt(ROSA)26Sortm1(HBEGF)Awai/Gt(ROSA)26Sor+ Tg(Krt1-15-cre/PGR)22Cot/0involves: C57BL/6J * SJL/J

cellular phenotype

digestive/alimentary phenotype

References

Additional References

Additional - Gt(ROSA)26Sortm1(HBEGF)Awai related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Gt(ROSA)26Sor^{tm1(HBEGF)Awai}

Allele Symbol: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}

Genotype: Cd19^tm1(cre)Cgn/? Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor^{tm1(HBEGF)Awai}
involves: 129P2/OlaHsd * C57BL/6

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor^{tm1(HBEGF)Awai} Tg(Gdf9-icre)5092Coo/0
involves: C57BL/6

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor⁺ Tg(Gh1-cre)bKnmn/0
involves: C57BL/6 * FVB/N

Genotype: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor⁺ Tg(Krt1-15-cre/PGR)22Cot/0
involves: C57BL/6J * SJL/J

Additional - Gt(ROSA)26Sor^{tm1(HBEGF)Awai} related