Overview

Also Known As: Tg^Pdx1

These Tg^Pdx1 mice express a transgene containing EGFP and Ipf1 after crossing with a strain expressing tetracycline-transactivator (tTA) under the control of a tissue-specific promoter. Such double mutant mice may be useful in studies of pancreatic endocrine/exocrine function and diabetes.

Donating Investigator

Raymond MacDonald, UTSW Medical Center

Genetic overview

Genetic Background	Generation

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Type
Transgenic (Reporter, Inducible, Inserted expressed sequence)

Gnat2^cpfl3

Allele Type	Gene Symbol	Gene Name
Spontaneous	Gnat2	guanine nucleotide binding protein, alpha transducing 2

View Genetics

Research Applications

Research Tools
Sensorineural Research
Metabolism Research
Endocrine Deficiency Research

View All Research Applications

Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Important Note

This strain may be homozygous for Gnat2^cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision.

Detailed Description

Mice hemizygous for the transgene are viable, fertile, normal in size, and do not display any behavioral abnormalities. At the Jackson Laboratory, no homozygous mice were produced from mating hemizygotes together, suggesting that homozygous transgenic animals die in utero. Expression of the bicistronic transgene is under the regulation of a tetracycline promoter element (TRE; tetO). By themselves, these transgenic mice do not express EGFP, but when these mice are mated with a second transgenic strain expressing tetracycline-transactivator (tTA) protein under the control of a tissue-specific promoter, Ipf1 and EGFP are highly expressed in the appropriate tissue of bitransgenic offspring.

This mouse was originally designed to be mated to an apancreatic targeted mutant with tTA_off in place of the endogenous Ipf1 gene (see Stock No. 005701). The combined mutations allow normal pancreatic development and function until doxycycline treatment renders the double mutant mouse conditionally null for Ipf1 expression. Using these double transgenic mice, pancreatic developmental can be arrested at any stage during embryonic development or in adult mice. Such double mutant mice may be useful in studies of pancreatic endocrine/exocrine function and diabetes. Tg(tetO-Ipf1,EGFP)956.6Macd transgenic mice also may be bred with other tTA transgenic strains for conditional mutation analysis.

Development

A bicistronic transgenic vector was generated containing an Ipf1 minigene (both exons linked with a shortened intron and preceded by a truncated 5' untranslated region) and an internal ribosome entry site-linked enhanced green fluorescent protein (EGFP) all under transcriptional control of a tetracycline-responsive regulatory element (TRE). Transgenic mice were generated by pronuclear injection of the construct into fertilized [C57BL/6 x SJL] F2 hybrid embryos. Two-cell stage eggs were implanted into pseudopregnant foster mothers. Founder line 956.6 was obtained and was maintained by transgenic positive sibling intercross. At some point, transgenic mice were bred to B6;129 mice with a targeted mutation. The targeted mutation was selected against in subsequent breedings, and the transgenic line was again maintained by hemizygous intercrosses prior to cryopreservation.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Transgenic mice do not express EGFP until a tetracycline-transactivator (tTA) protein is introduced; after which point Ipf1 and EGFP from the transgene are highly expressed. Transgenic mice have low level transgene expression (mRNA) in liver, kidney, spleen, and salivary gland.
Site of Expression

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Holland AM; Hale MA; Kagami H; Hammer RE; MacDonald RJ. 2002. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99(19):12236-41PubMed: 12221286 MGI: J:79206

View All References

Genetics

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Symbol: Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Name	transgene insertion 956-6, Raymond J MacDonald
Allele Type	Transgenic (Reporter, Inducible, Inserted expressed sequence)
Allele Synonym(s)	Tg(tetO-Ipf1,EGFP)956.6Macd; transgene insertion 956-6, Raymond J MacDonald
Gene Symbol and Name	Tg(tetO-Ipf1,EGFP)956.6Macd, transgene insertion 956-6, Raymond J MacDonald
Gene Synonym(s)	Pdx1-EGFP; Pdx1-GFP; Pdx1^Tg; Tg^Pdx1; tTA-responsive Pdx1-EGFP; tetO-Pdx1; tetO-Pdx1/EGFP; tetO-Pdx1-EGFP; tetO/Pdx1/EGFP
Promoter	tetO, tet operator,
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Transgenic mice do not express EGFP until a tetracycline-transactivator (tTA) protein is introduced; after which point Ipf1 and EGFP from the transgene are highly expressed. Transgenic mice have low level transgene expression (mRNA) in liver, kidney, spleen, and salivary gland.
Strain of Origin	(C57BL/6 x SJL)F2
Chromosome	UN
Molecular Note	A transgenic vector containing an Ipf1 minigene (both exons of Ipf1 linked by a shortened exon and preceded by a truncated 5' UTR and an IRES-linked EGFP reporter) under control of seven direct repeats of the tetracycline operator (tetO) fused to the human cytomegalovirus (hCMV) immediate early promoter. High expression of Ipf1 and EGFP is induced by introduction of the tetracycline-transactivator protein by breeding with an appropriate mouse line.
Mutations Made By	Raymond MacDonald, UTSW Medical Center

Gnat2^cpfl3

Allele Symbol: Gnat2^cpfl3

Allele Name	cone photoreceptor function loss 3
Allele Type	Spontaneous
Allele Synonym(s)	cone photoreceptor function loss 3; Gnat2^cpfl3
Gene Symbol and Name	Gnat2, guanine nucleotide binding protein, alpha transducing 2
Gene Synonym(s)	ACHM4; expressed sequence AW490837; Gt-2; Gnat-2; Tcalpha; Gnat-2; GNATC; AW490837
Strain of Origin	various
Chromosome	3
General Note	This allele has been detected in the following strains either by genotyping or complementation testing: ALS/LtJ, SENCARA/PtJ, SENCARB/PtJ, SENCARC/PtJ, PN/nBSwUmabJ. (J:122428) The allele has also been reported in NMRI and CD1 (Lluis Montoliu, J:212307)
Molecular Note	A single nucleotide substitution of G to A at position 598 in exon 6. This mutation converts codon 200 from aspartic acid to asparagine.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Tissue/Cell Markers
  - Tissue/Cell Markers: pancreatic beta cells
  - Mutagenesis and Transgenesis: Tetop Tet System
  - Tissue/Cell Markers: multiple
- Fluorescent Proteins
- Endocrine Deficiency Research
- Tet Expression Systems
  - tTA/rtTA Responsive Strains
Metabolism Research
- Enzyme Deficiency
  - exocrine pancreatic insufficiency
Endocrine Deficiency Research
- Pancreas Defects

Genotype: Gnat2^cpfl3 related

Sensorineural Research
- Eye Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

cellular phenotype

increased cell proliferation
- foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment

homeostasis/metabolism phenotype

decreased circulating glucose level
- 14 days after doxycycline withdrawal after 14 days of treatment resulted in a significant decrease in blood glucose levels with 4/5 mice becoming normoglycemic by 28 days

decreased insulin secretion
- there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

impaired glucose tolerance
- adult transgenic rescue animals treated with doxycycline for 14 days exhibit a defective response to glucose challenge compared to wild-type, non mutant transgenic, or untreated rescue mice
- cose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes
- when adult mice are treated with doxycycline for 0, 7, 14, or 21 days, mice show an increased early glucose response within 7 days of start of treatment and ability to recover from glucose challenge is impaired compared to untreated transgenics where glucose levels recover to basal levels within 3 hours; by 14 days of doxycycline treatment, mice have diabetes

increased circulating glucose level
- with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels

increased glucagon secretion
- in doxycycline-treated mice there is an increase in glucagons-positive cells

endocrine/exocrine gland phenotype

abnormal pancreas development
- d with no acinar or islet tissue
- pancreas of transgenic rescue newborn mice is 50% the size of a normal wild-type neonatal pancreas
- treatment of pregnant mice with doxycycline from the first day of pregnancy through parturition prevents formation of the pancreas in mice with the transgenic rescue genotype
- treatment on E11.5 arrests pancreatic development ~36 hours later; at birth the underdeveloped remnant consisted of a large and extended duct with several terminal, aborted, ductal buds with ducts lined with a single layer of primitive epithelial cells and with no acinar or islet tissue

abnormal pancreatic beta cell morphology
- after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin

decreased insulin secretion
- there is a marked reduction in insulin in pancreata of doxycycline-treated mice; after withdrawal of doxycycline, insulin +ve cells are detected in islets of smaller islet-like cell clusters

increased glucagon secretion
- in doxycycline-treated mice there is an increase in glucagons-positive cells

small pancreatic islets
- after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type

References

Holland AM; Hale MA; Kagami H; Hammer RE; MacDonald RJ. 2002. Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99(19):12236-41PubMed: 12221286 MGI: J:79206

Additional References

Chang B; Dacey MS; Hawes NL; Hitchcock PF; Milam AH; Atmaca-Sonmez P; Nusinowitz S; Heckenlively JR. 2006. Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci 47(11):5017-21PubMed: 17065522 MGI: J:122428

Additional - Gnat2^cpfl3 related

Additional - Tg(tetO-Ipf1,EGFP)956.6Macd related

Technical Support

Contact Technical Support

Genotyping Protocols
- MELT: Tg(tetO-Ipf1,EGFP)956.6Macd
- Standard PCR: Fluorescent Proteins (Generic GFP)
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygous mice are bred to wildtype siblings. When mating hemizygous mice together at The Jackson Laboratory, none of the 48 pups sampled were homozygous, indicating that homozygotes are not viable.
- Additional Breeding and Husbandry Support
Mating System
- +/+ sibling x Hemizygote
Citation
When using the Tg^Pdx1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #005699 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(tetO-Ipf1,EGFP)956.6Macd

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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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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Also Known As: TgPdx1

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(tetO-Ipf1,EGFP)956.6Macd

Allele Symbol: Tg(tetO-Ipf1,EGFP)956.6Macd

Gnat2cpfl3

Allele Symbol: Gnat2cpfl3

Disease Terms

Research Areas By Genotype

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

Genotype: Gnat2cpfl3 related

Mammalian Phenotype Terms by Genotype

Genotype: Pdx1tm1Macd/Pdx1tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

cellular phenotype

homeostasis/metabolism phenotype

endocrine/exocrine gland phenotype

References

Additional References

Additional - Gnat2cpfl3 related

Additional - Tg(tetO-Ipf1,EGFP)956.6Macd related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Tg^Pdx1

Gnat2^cpfl3

Allele Symbol: Gnat2^cpfl3

Genotype: Gnat2^cpfl3 related

Genotype: Pdx1^tm1Macd/Pdx1^tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Additional - Gnat2^cpfl3 related