Strain Name:

B6.129S6-Pasktm1Weng/J

Stock Number:

017709

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Availability:

Cryopreserved - Ready for recovery

The Pask gene is disrupted by the insertion of an IRES-β-geo fusion cassette in these knockin/knockout mice. LacZ is detected in testis and homozygotes exhibit a range of metabolic traits.

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 Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationMM080850pN1
Generation Definitions
 
Donating Investigator Roland Wenger,   University of Zurich

Description
A splice acceptor site and an IRES-β-geo fusion cassette replace exons 10-14 of the PAS domain containing serine/threonine kinase (Pask) gene in these mutant mice. Gene function is abolished. PASK is a serine/threonine kinase which regulates energy homeostasis and acts as a cellular metabolic sensor. In wildtype mice, PASK is expressed in post-meiotic germ cells during spermatogenesis, with typically low level ubiquitous expression. Homozygous Pask-/- mice are viable, fertile, and normal in size, with lacZ staining visible in the testis beginning at 25 days of age. These mice exhibit impaired glucose-stimulated insulin secretion with no change in islet size or morphology. Increased O2 consumption, CO2 production, and heat generation is also observed. On a high-fat diet, Pask-/- mice have reduced liver triglyceride levels and show little difference in glucose tolerance, insulin resistance, or weight gain compared to wildtype mice.

Development
A targeting vector was designed to replace exons 10-14 of the PAS domain containing serine/threonine kinase (Pask) gene with a splice acceptor site, an internal ribosome entry site (IRES), and a neomycin-β-galactosidase fusion protein (β-geo). The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into (C57BL/6 x DBA)F1 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed at least 10 generations to C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Pasktm1Weng/Pasktm1Weng

        B6.129S6-Pasktm1Weng
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis   (MGI Ref ID J:125307)
    • decreased circulating insulin level
      • insulin levels are modestly but significantly lower at 5 and 45 minutes after a glucose injection   (MGI Ref ID J:125307)
      • when fed a high fat diet, fasting insulin levels are significantly lower than in controls   (MGI Ref ID J:125307)
    • decreased insulin secretion
      • total insulin secreted by isolated islets of Langerhans in response to glucose stimulation is 56% that of wild-type islets   (MGI Ref ID J:125307)
    • improved glucose tolerance
      • when fed a high fat diet mice do not develop glucose intolerance unlike wild-type mice   (MGI Ref ID J:125307)
      • however, on a standard diet there is no significant difference in glucose tolerance in mutants compared to wild-type mice   (MGI Ref ID J:125307)
    • increased insulin sensitivity
      • when fed a high fat diet mice do not develop insulin resistance unlike wild-type mice   (MGI Ref ID J:125307)
      • however, on a standard diet there is no significant difference in insulin sensitivity in mutants compared to wild-type mice   (MGI Ref ID J:125307)
  • abnormal metabolism
    • produce more CO2 and heat   (MGI Ref ID J:125307)
  • abnormal respiratory quotient
    • respiratory quotient indicates a slight substrate preference for carbohydrate over fat   (MGI Ref ID J:125307)
  • decreased susceptibility to diet-induced obesity
    • when fed a high fat diet   (MGI Ref ID J:125307)
  • increased oxygen consumption   (MGI Ref ID J:125307)
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype
    • despite defects in glucose-stimulated insulin secretion, no defects are detected in islet of Langerhans morphology, size or beta-cell area and no differences in total pancreatic insulin levels are seen   (MGI Ref ID J:125307)
    • decreased insulin secretion
      • total insulin secreted by isolated islets of Langerhans in response to glucose stimulation is 56% that of wild-type islets   (MGI Ref ID J:125307)
  • growth/size/body phenotype
  • decreased susceptibility to diet-induced obesity
    • when fed a high fat diet   (MGI Ref ID J:125307)
  • liver/biliary system phenotype
  • decreased susceptibility to hepatic steatosis
    • when fed a high fat diet   (MGI Ref ID J:125307)
  • muscle phenotype
  • abnormal muscle physiology
    • permeabilized soleus muscle fibers show elevated ATP production from succinate   (MGI Ref ID J:125307)
    • however, no difference in mitochondrial number or area are detected in soleus muscles   (MGI Ref ID J:125307)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • despite increased metabolism and resistance to diet induce obesity, no differences in locomotor activity or food intake are detected   (MGI Ref ID J:125307)
  • respiratory system phenotype
  • abnormal pulmonary ventilation
    • hypoxic ventilatory response (HVR) is increased in females throughout exposure to 10% or 8% O2 relative to controls   (MGI Ref ID J:139216)
    • in males HVR is increased relative to controls only during the first minute of exposure to 8% O2   (MGI Ref ID J:139216)
    • hypoxic ventilatory decline is slower in males at 8% and in females at 8% and 10% O2 relative to sex-matched controls   (MGI Ref ID J:139216)
    • females show impaired ventilatory acclimatization following exposure to acute hypoxia   (MGI Ref ID J:139216)
  • nervous system phenotype
  • abnormal nervous system physiology
    • males have lower tyrosine hydroxylase activity in the pontine (A5 and A6) and medullary (A2C2) brain stem catecholaminergic cell groups compared to sex matched controls   (MGI Ref ID J:139216)
    • females have higher tyrosine hydroxylase activity in the pontine (A5 and A6) and medullary (A2C2 and A1C1) brain stem catecholaminergic cell groups compared to sex matched controls   (MGI Ref ID J:139216)

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

Pasktm1Weng/Pasktm1Weng

        involves: 129S6/SvEvTac * C57BL/6
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • mice are fertile and show no abnormalities pertaining to spermatogenesis or sperm motility   (MGI Ref ID J:85762)
View Research Applications

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

Diabetes and Obesity Research

Metabolism Research

Reproductive Biology Research

Research Tools
lacZ Expression
Diabetes and Obesity Research
      lacZ

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pasktm1Weng
Allele Name targeted mutation 1, Roland H Wenger
Allele Type Targeted (Null/Knockout, Reporter)
Common Name(s) PASK-; Paskin-;
Mutation Made By Roland Wenger,   University of Zurich
Strain of Origin129S6/SvEvTac
Site of ExpressionlacZ staining visible in the testis beginning at 25 days of age.
Gene Symbol and Name Pask, PAS domain containing serine/threonine kinase
Chromosome 1
Gene Common Name(s) PASKIN; STK37; mKIAA0135;
Molecular Note Exons 10 through 14 were replace with a cassette containing a splice acceptor site and IRES-beta-geo. Norhtern blot analysis of various tissues confirmed the absence of endogenous transcript and identified mutant transcript containing the beta-geo squenence. [MGI Ref ID J:85762]

Genotyping

Genotyping Information

Genotyping Protocols

Pasktm1Weng,

Separated MCA



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Katschinski DM; Marti HH; Wagner KF; Shibata J; Eckhardt K; Martin F; Depping R; Paasch U; Gassmann M; Ledermann B; Desbaillets I; Wenger RH. 2003. Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN. Mol Cell Biol 23(19):6780-9. [PubMed: 12972598]  [MGI Ref ID J:85762]

Additional References

Pasktm1Weng related

Borter E; Niessen M; Zuellig R; Spinas GA; Spielmann P; Camenisch G; Wenger RH. 2007. Glucose-stimulated insulin production in mice deficient for the PAS kinase PASKIN. Diabetes 56(1):113-7. [PubMed: 17192472]  [MGI Ref ID J:121974]

Hao HX; Cardon CM; Swiatek W; Cooksey RC; Smith TL; Wilde J; Boudina S; Abel ED; McClain DA; Rutter J. 2007. PAS kinase is required for normal cellular energy balance. Proc Natl Acad Sci U S A 104(39):15466-71. [PubMed: 17878307]  [MGI Ref ID J:125307]

Soliz J; Soulage C; Borter E; van Patot MT; Gassmann M. 2008. Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice. Am J Physiol Regul Integr Comp Physiol 295(2):R649-58. [PubMed: 18509100]  [MGI Ref ID J:139216]

da Silva Xavier G; Farhan H; Kim H; Caxaria S; Johnson P; Hughes S; Bugliani M; Marselli L; Marchetti P; Birzele F; Sun G; Scharfmann R; Rutter J; Siniakowicz K; Weir G; Parker H; Reimann F; Gribble FM; Rutter GA. 2010. Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion. Diabetologia :. [PubMed: 21181396]  [MGI Ref ID J:167207]

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

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3300.00
Animals Provided

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 on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4290.00
Animals Provided

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 on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  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.
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