Strain Name:

STOCK Pdx1tm1Macd/J

Stock Number:

005701

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Purchasing Information

Description

Strain Information

Former Names STOCK Ipf1tm1Macd/J    (Changed: 15-DEC-06 )
Type Mutant Stock; Targeted Mutation;
Specieslaboratory mouse
 
Donating Investigator Raymond MacDonald,   UTSW Medical Center

Description
Mice homozygous for the targeted mutation fail to develop a pancreas. Heterozygous mice have normal pancreas development but partially impaired glucose tolerance in adulthood. The substitution of the targeted gene with tTAoff inactivates the endogenous allele and places tTAoff expression under the control of the endogenous transcriptional regulatory sequences. tTA expression from the modified locus is identical to that of the normal allele; tTA mRNA is detectable in the pancreas but not in other visceral organs or salivary glands. This mutant may be useful in studies of pancreatic endocrine/exocrine function and diabetes. Heterozygotes also can be bred with transgenic mice that express a target gene under the regulation of a tetracycline-responsive element (TRE; tetO) for pancreas-specific applications.

This mutant was originally designed to be mated with mutant mice with a TRE-controlled transgene coding for the endogenous Pdx1 (Ipf1) gene along with a reporter (EGFP or beta-galactosidase gene, (see Stock No. 005699 and 005728 respectively).

Development
A targeting vector containing a tetracycline-responsive tet-repressor/VP16 fusion transactivator (tTAoff) and the neomycin-resistance gene flanked with 4.5-kb upstream and 1.3-kb downstream homology domains was used to replace the entire coding region (both exons and the intron) of the endogenous Pdx1 locus. The construct was electroporated into the (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred with C57BL/6 females to generate heterozygotes. At some point, mutant mice were bred to B6SJL hybrid transgenic mice. The transgene was selected against in subsequent breedings, and strain is now maintained as heterozygous for the Pdx1 targeted mutation.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pdx1
005699   STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J
005728   STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
View Strains carrying other alleles of Pdx1     (2 strains)

Additional Web Information

Tet Expression Systems

Phenotype

Phenotype Information

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Pdx1tm1Macd/Pdx1+

        involves: 129S1/Sv * 129X1/SvJ
  • homeostasis/metabolism phenotype
  • impaired glucose tolerance (MGI Ref ID J:79206)
    • heterozygotes display partially impaired glucose tolerance compared to wild-type mice; doxycycline treatment has no effect
    • heterozygotes display partially impaired early response to glucose challenge compared to wild-type mice; ability to recover after glucose challenge is impaired

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 islet of Langerhans morphology (MGI Ref ID J:101742)
    • after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
    • 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
  • 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
  • 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
  • digestive/alimentary phenotype
  • abnormal islet of Langerhans morphology (MGI Ref ID J:101742)
    • after dox treatment for 14 days, there is a significant decrease in islet area compared to wild-type
    • 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
  • 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
  • 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
  • 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

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

Research Applications

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

Endocrine Deficiency Research
Pancreas Defects

Metabolism Research
Enzyme Deficiency (exocrine pancreatic insufficiency)

Research Tools
Endocrine Deficiency Research
Genetics Research (Tissue/Cell Markers: multiple)
Genetics Research (Tissue/Cell Markers: pancreatic beta cells)
Tet Expression Systems (tTA/rtTA Expressing Strains)

Genes & Alleles

Gene & Allele Information

Allele Symbol Pdx1tm1Macd
Allele Name targeted mutation 1, Raymond J MacDonald
Common Name(s) Pdx1tTA;
Mutation Made By Raymond MacDonald,   UTSW Medical Center
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Site of ExpressionExpresses tTA in pancreas.
Gene Symbol and Name Pdx1, pancreatic and duodenal homeobox 1
Chromosome 5
Gene Common Name(s) GSF; IDX-1; IPF-1; IPF1; IUF1; Idx1; Ipf1; MODY4; PDX-1; STF-1; Stf1; insulin promoter factor 1; insulin promoter factor 1, homeodomain transcription factor; pancreatic and duodenal homeobox gene 1;
Molecular Note Exons 1 and 2, which encompass the entire coding region, were replaced with a cassette containing a tetracycline transactivator (tTA) and a neo resistance gene. RT-PCR showed tTA expression in adult pancreas tissue but not in other visceral organs or salivary glands. [MGI Ref ID J:79206]

Genotyping

Genotyping Information

Genotyping Protocols

Pdx1tm1Macd, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

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

Pdx1tm1Macd related

Brennand K; Huangfu D; Melton D. 2007. All beta Cells Contribute Equally to Islet Growth and Maintenance. PLoS Biol 5(7):e163. [PubMed: 17535113]  [MGI Ref ID J:124045]

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]

Stanger BZ; Datar R; Murtaugh LC; Melton DA. 2005. Direct regulation of intestinal fate by Notch. Proc Natl Acad Sci U S A 102(35):12443-8. [PubMed: 16107537]  [MGI Ref ID J:101154]

Stanger BZ; Tanaka AJ; Melton DA. 2007. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130):886-91. [PubMed: 17259975]  [MGI Ref ID J:118596]

Wang S; Hecksher-Sorensen J; Xu Y; Zhao A; Dor Y; Rosenberg L; Serup P; Gu G. 2008. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Dev Biol 317(2):531-40. [PubMed: 18394599]  [MGI Ref ID J:136131]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are maintained as heterozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
Cryopreserved Embryos Fee $1600.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
Cryopreserved Embryos Fee $2080.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Control Information

  Control
   Wild-type from the colony
 
  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.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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