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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System +/+ sibling x Hemizygote (Female x Male) 13-SEP-08 Species laboratory mouse Generation ?+N1p Donating Investigator Raymond MacDonald, UTSW Medical Center Important Note
This strain may be homozygous for Gnat2cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision.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 tTAoff 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.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
003072 ALS/LtJ 006180 CD10/JlsJ 005052 PN/nBSwUmabJ 002746 SENCARA/PtJ 002747 SENCARB/PtJ 002748 SENCARC/PtJ 006135 STOCK Sgk3fz-ica/McirJ 003773 STOCK Tg(CAG-ECFP)CK6Nagy/J 005645 STOCK Tg(CAG-mRFP1)1F1Hadj/J 004623 STOCK Tg(Fos-lacZ)34Efu/J 005667 STOCK Tg(Neurog3-cre)C1Able/J 003262 STOCK Tg(Trp53A135V)L3Ber/J 005104 STOCK Tg(tetO-HIST1H2BJ/GFP)47Efu/J
005701 STOCK Pdx1tm1Macd/J 005728 STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Tet Expression Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Pdx1tm1Macd/Pdx1tm1Macd Tg(tetO-Ipf1,EGFP)956.6Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
- homeostasis/metabolism phenotype
- decreased circulating glucose level (MGI Ref ID J:101742)
- 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
- impaired glucose tolerance (MGI Ref ID J:79206)
- 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
- 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 (MGI Ref ID J:79206)
- with doxycycline treatment for 21 day, adult rescue mice show a 4-fold increase in fasting blood glucose to diabetic levels
- endocrine/exocrine gland phenotype
- abnormal pancreas development (MGI Ref ID J:79206)
- 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 (MGI Ref ID J:101742)
- after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin
- decreased insulin secretion (MGI Ref ID J:101742)
- 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 (MGI Ref ID J:101742)
- in doxycycline-treated mice there is an increase in glucagons-positive cells
- small pancreatic islets (MGI Ref ID J:101742)
- after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
- digestive/alimentary phenotype
- abnormal pancreas development (MGI Ref ID J:79206)
- 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 (MGI Ref ID J:101742)
- after 14 or 28 days of dox treatment there are, still present, beta cells which lack insulin
- decreased insulin secretion (MGI Ref ID J:101742)
- 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 (MGI Ref ID J:101742)
- in doxycycline-treated mice there is an increase in glucagons-positive cells
- small pancreatic islets (MGI Ref ID J:101742)
- after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
- cellular phenotype
- increased cell proliferation (MGI Ref ID J:101742)
- foci of duct proliferation are present in mice after 14 days of doxycycline treatment and become more prominent with continued treatment
This mouse can be used to support research in many areas including:
GFP relatedEndocrine Deficiency Research
Pancreas Defects
Metabolism Research
Enzyme Deficiency
exocrine pancreatic insufficiency
Research Tools
Endocrine Deficiency Research
Fluorescent Proteins
Genetics Research
Mutagenesis and Transgenesis: Tetop Tet System
Tissue/Cell Markers: multiple
Tissue/Cell Markers: pancreatic beta cells
Tet Expression Systems
tTA/rtTA Responsive Strains
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO-Ipf1,EGFP)956.6Macd | ||
|---|---|---|---|
| Allele Name | transgene insertion 956-6, Raymond J MacDonald | ||
| Allele Type | Transgenic (Reporter) | ||
| Common Name(s) | Pdx1-EGFP; Pdx1-GFP; Pdx1Tg; TgPdx1; tTA-responsive Pdx1-EGFP; tetO-Pdx1; tetO-Pdx1-EGFP; tetO-Pdx1/EGFP; tetO/Pdx1/EGFP; | ||
| Mutation Made By | Raymond MacDonald, UTSW Medical Center | ||
| Strain of Origin | (C57BL/6 x SJL)F2 | ||
| 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. | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Expressed Gene | Pdx1, pancreatic and duodenal homeobox 1, mouse, laboratory | ||
| Promoter | tetO, tet operator, | ||
| 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. [MGI Ref ID J:79206] | ||
| Gene Symbol and Name | Tg(tetO-Ipf1,EGFP)956.6Macd, transgene insertion 956-6, Raymond J MacDonald | ||
| Chromosome | UN | ||
| Gene Common Name(s) | Pdx1-EGFP; Pdx1-GFP; Pdx1Tg; TgPdx1; tTA-responsive Pdx1-EGFP; tetO-Pdx1; tetO-Pdx1-EGFP; tetO-Pdx1/EGFP; tetO/Pdx1/EGFP; | ||
| Allele Symbol | Gnat2cpfl3 | ||
| Allele Name | cone photoreceptor function loss 3 | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | Gnat2; | ||
| Strain of Origin | various | ||
| Gene Symbol and Name | Gnat2, guanine nucleotide binding protein, alpha transducing 2 | ||
| Chromosome | 3 | ||
| Gene Common Name(s) | ACHM4; AW490837; GNATC; Gnat-2; Gt-2; Tcalpha; expressed sequence AW490837; | ||
| 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) Phenotypic Similarity to Human Syndrome in Orthologous Human Gene: OMIM +139340 ACHROMATOPSIA 4. | ||
| Molecular Note | A single nucleotide substitution of G to A at position 598 in exon 6. This mutation converts codon 200 from apartic acid to asparagine. [MGI Ref ID J:122428] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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):12236-41. [PubMed: 12221286] [MGI Ref ID 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):5017-21. [PubMed: 17065522] [MGI Ref ID J:122428]
Gnat2cpfl3 relatedTg(tetO-Ipf1,EGFP)956.6Macd relatedAlexander JJ; Umino Y; Everhart D; Chang B; Min SH; Li Q; Timmers AM; Hawes NL; Pang JJ; Barlow RB; Hauswirth WW. 2007. Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13(6):685-7. [PubMed: 17515894] [MGI Ref ID J:121897]
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):5017-21. [PubMed: 17065522] [MGI Ref ID J:122428]
Deng WT; Sakurai K; Liu J; Dinculescu A; Li J; Pang J; Min SH; Chiodo VA; Boye SL; Chang B; Kefalov VJ; Hauswirth WW. 2009. Functional interchangeability of rod and cone transducin alpha-subunits. Proc Natl Acad Sci U S A 106(42):17681-6. [PubMed: 19815523] [MGI Ref ID J:153749]
Nusinowitz S; Ridder WH rd; Ramirez J. 2007. Temporal response properties of the primary and secondary rod-signaling pathways in normal and Gnat2 mutant mice. Exp Eye Res 84(6):1104-14. [PubMed: 17408617] [MGI Ref ID J:126462]
Umino Y; Solessio E; Barlow RB. 2008. Speed, spatial, and temporal tuning of rod and cone vision in mouse. J Neurosci 28(1):189-98. [PubMed: 18171936] [MGI Ref ID J:131050]
Gauthier BR; Wiederkehr A; Baquie M; Dai C; Powers AC; Kerr-Conte J; Pattou F; MacDonald RJ; Ferrer J; Wollheim CB. 2009. PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. Cell Metab 10(2):110-8. [PubMed: 19656489] [MGI Ref ID J:151308]
Hale MA; Kagami H; Shi L; Holland AM; Elsasser HP; Hammer RE; MacDonald RJ. 2005. The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas. Dev Biol 286(1):225-37. [PubMed: 16126192] [MGI Ref ID J:103522]
Holland AM; Gonez LJ; Naselli G; Macdonald RJ; Harrison LC. 2005. Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas. Diabetes 54(9):2586-95. [PubMed: 16123346] [MGI Ref ID J:101742]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry 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. Mating System +/+ sibling x Hemizygote (Female x Male) 13-SEP-08
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 Cryopreserved Embryos $1600.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 Cryopreserved Embryos $2080.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
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| Important Note | |
| This strain may be homozygous for Gnat2cpfl3, cone photoreceptor function loss 3, which affects bright light (photopic) vision. | |
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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. | ||
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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.Ordering and Purchasing Information
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