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Type Mutant Stock; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p Donating Investigator Raymond MacDonald, UTSW Medical Center Description
Hemizygous transgenic mice are viable, fertile, normal in size, and do not display any behavioral abnormalities. Expression of the bicistronic transgene is under the regulation of a tetracycline-responsive promoter element (TRE; tetO). When transgenic mice are bred to a second transgenic strain expressing tetracycline-transactivator (tTA) protein under the control of a tissue-specific promoter, the bitransgenic offspring express Ipf1 and lacZ in the appropriate target tissue. Further, Ipf1 and lacZ expression in bitransgenic mice can be suppressed by administration of the tetracycline analog, doxycycline. All cells expressing Ipf1 coexpress the reporter, and mRNA levels of the transgenic and endogenous Ipf1 fluctuate in concert during development.This mouse was designed originally to be mated to an pancreatic targeted mutant with tTAoff in place of the 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. In these double transgenic animals, pancreatic developmental can be arrested at stage during embyronic development or in adult mice. Such double mutant mice may be useful in studies of pancreatic endocrine/exocrine function and diabetes. Tg(tetO-Ipf1,lacZ)958.1Macd transgenic mice also may be bred with other tTA 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 beta-galactosidase (lacZ) 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] F1 hybrid embyros. Two-cell stage eggs were implanted into pseudopregnant foster mothers. Founder line 958.1 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.
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| Noncarrier | ||
| Considerations for Choosing Controls | ||
lacZ Expression Strains
View lacZ Expression Strains (186 strains)
Strains carrying other alleles of Pdx1
005701 STOCK Pdx1tm1Macd/J 005699 STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J View Strains carrying other alleles of Pdx1 (2 strains)
Strains carrying other alleles of lacZ
View Strains carrying other alleles of lacZ (43 strains)
Strains carrying other alleles of tetO
View Strains carrying other alleles of tetO (36 strains)
Fluorescent Proteins/lacZ Systems
Tet Expression Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
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,lacZ)958.1Macd/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
- homeostasis/metabolism phenotype
- impaired glucose tolerance (MGI Ref ID J:103522)
- transgenic mice gradually attain an impaired glucose tolerance response to glucose challenge
- endocrine/exocrine gland phenotype
- abnormal pancreas development (MGI Ref ID J:103522)
- when dams are treated with doxycycline from conception through birth, only small epithelial remnants of the pancreas form; treatment at E7.5 or E8.5 results in the same phenotype
- doxycycline from E9.5 diminishes epithelial morphogenesis; treatement from E9.5 allows outgrowth of a linear epithelial tube with nascent invaginations representing initial primary branching
- treatment from E11.5 allows the formation of a larger crude duct-like structure with a few distal primary branches; treatement from E12.5 permits formation of extensive fine structure consisting of immature acini and associated small ductules
- with treatment from E12.5, pancreatic dorsal and ventral remnants composed of convoluted partially branched duct-like epithelium of columnar epithelium are present, and show a block at the stage of acinar cell formation
- examination of embryo ductal remnants from mice treated with dox from E11.5 show an absence of preacini; treatment from E12.5 results in a larger remnant with a smaller proportion of primitive duct; the epithelium is replaced by numerous eosinophilic clusters lacking ductal markers which are polarized, arranged around a central lumen and resemble immature acini
- absent pancreas (MGI Ref ID J:103522)
- ~1/5 pups are born without a pancreas; rescue of pancreas formation is observed in ~80% of transgenic mice
- digestive/alimentary phenotype
- abnormal pancreas development (MGI Ref ID J:103522)
- when dams are treated with doxycycline from conception through birth, only small epithelial remnants of the pancreas form; treatment at E7.5 or E8.5 results in the same phenotype
- doxycycline from E9.5 diminishes epithelial morphogenesis; treatement from E9.5 allows outgrowth of a linear epithelial tube with nascent invaginations representing initial primary branching
- treatment from E11.5 allows the formation of a larger crude duct-like structure with a few distal primary branches; treatement from E12.5 permits formation of extensive fine structure consisting of immature acini and associated small ductules
- with treatment from E12.5, pancreatic dorsal and ventral remnants composed of convoluted partially branched duct-like epithelium of columnar epithelium are present, and show a block at the stage of acinar cell formation
- examination of embryo ductal remnants from mice treated with dox from E11.5 show an absence of preacini; treatment from E12.5 results in a larger remnant with a smaller proportion of primitive duct; the epithelium is replaced by numerous eosinophilic clusters lacking ductal markers which are polarized, arranged around a central lumen and resemble immature acini
- absent pancreas (MGI Ref ID J:103522)
- ~1/5 pups are born without a pancreas; rescue of pancreas formation is observed in ~80% of transgenic mice
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
lacZ relatedEndocrine Deficiency Research
Pancreas Defects
Metabolism Research
Enzyme Deficiency
exocrine pancreatic insufficiency
Research Tools
lacZ Expression
Diabetes and Obesity Research
lacZ
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
lacZ Expression
| Allele Symbol | Tg(tetO-Ipf1,lacZ)958.1Macd | ||
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| Allele Name | transgene insertion 958-1, Raymond J MacDonald | ||
| Allele Type | Transgenic (Reporter) | ||
| Common Name(s) | Pdx1-nlacZ; TgPdx1-lacZ; TgPdx1-nlacZ; TgPdx1; tetO-Pdx1; tetO-Pdx1-nlacZ; tetO-Pdx1/lacZ; tetO-Pdx1/nlacZ; | ||
| Mutation Made By | Raymond MacDonald, UTSW Medical Center | ||
| Strain of Origin | (C57BL/6 x SJL)F2 | ||
| Site of Expression | When crossed with a strain expressing tTA, bitransgenic progeny express the transgene in the target tissue. Expression of the transgene can be suppressed by the administration of tetracycline or its analog, doxycyline. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Expressed Gene | Pdx1, pancreatic and duodenal homeobox 1, mouse, laboratory | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note | A transgenic vector was generated containing an Ipf1 minigene (both exons linked with a shortened intron). The Ipf1 gene was preceded by a truncated 5' UTR and an IRES-linked beta-galactosidase (lacZ) gene under transcriptional control of 7 direct repeats of the tetracycline operator sequence (tetO) fused to the human cytomegalovirus immediate-early promoter. [MGI Ref ID J:103522] | ||
| Gene Symbol and Name | Tg(tetO-Ipf1,lacZ)958.1Macd, transgene insertion 958-1, Raymond J MacDonald | ||
| Chromosome | UN | ||
| Gene Common Name(s) | Pdx1-nlacZ; TgPdx1-lacZ; TgPdx1-nlacZ; TgPdx1; tetO-Pdx1; tetO-Pdx1-nlacZ; tetO-Pdx1/lacZ; tetO-Pdx1/nlacZ; | ||
Genotyping Protocols
Generic LacZ Melt Curve Analysis, Melt Curve Analysis
Generic LacZ QPCR, QPCR
Generic LacZ, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are maintained as hemizygotes by transgenic positive sibling intercross.
| Pricing for USA, Canada and Mexico shipping destinations |
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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.
| Pricing for International shipping destinations |
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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.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
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| 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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