Strain Name:

B6.129(Cg)-Pnliptm1Dyh/J

Stock Number:

008884

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Availability:

Cryopreserved - Ready for recovery

These mice harbor a targeted "null" mutation of the Pnlip (pancreatic lipase [also called pancreatic triglyceride lipase or PTL]) gene and may be useful in studying the role of pancreatic lipolytic enzymes/triglyceride hydrolysis in lipid digestion, lipid transport, cholesterol metabolism, and fat absorption in the intestinal lumen.

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; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
GenerationN15pN1
Generation Definitions
 
Donating Investigator David Y Hui,   University of Cincinnati - GRI

Description
These mice harbor a null mutation of the Pnlip (pancreatic lipase [also called pancreatic triglyceride lipase or PTL]) gene. Homozygous (PTL-/-) mice are viable and fertile, with no protein expression from the targeted allele observed in pancreatic tissue extracts. Homozygotes exhibit mildly delayed triglyceride (also called triacylglycerol or TAG) absorption after low fat diet feeding, but significantly delayed TAG absorption on a high fat/high cholesterol diet. Homozygous mice have a significant decrease in the rate/amount of cholesterol absorption; attributed to PTL-deficiency delaying dietary fat absorption to the distal small intestine (ileum) where intestinal cholesterol uptake is less efficient. Because PLT-/- mice retain endogenous Cel (carboxyl ester lipase [also called cholesterol esterase]) expression, pancreatic extracts from PTL-/- mice retain robust TAG hydrolytic activity (albeit at lower levels than wildtype mice). This TAG hydrolytic activity is dependent on the presence of taurocholate (whereas taurodeoxycholate was found to be ineffective); consistent with the trihdroxy-, but not dihydroxy-, bile salt dependence of CEL. These PTL-/- mutant mice may be useful in studying the role of pancreatic lipolytic enzymes/triglyceride hydrolysis in lipid digestion, lipid transport, cholesterol metabolism, and fat absorption in the intestinal lumen.

Development
A targeting vector was designed to insert a thymidine kinase promoter- driven neomycin-resistant gene into exon 4 of the targeted gene, disrupting the targeted gene upstream of the domains required for endogenous enzymatic activity. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred with Black Swiss mice to establish the mutant colony. These PTL-mutant mice were subsequently backcrossed to C57BL/6J for at least 15 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. During the backcross, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Pancreatic Lipase Deficiency; PNLIPD   (PNLIP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Pnliptm1Dyh/Pnliptm1Dyh

        B6.129-Pnliptm1Dyh
  • digestive/alimentary phenotype
  • abnormal feces composition
    • 45% decrease in the amount of cholesterol in feces collected over a 24 hour period, indicating decreased absorption of cholesterol through the intestine   (MGI Ref ID J:86414)
  • abnormal intestinal lipid absorption
    • mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption   (MGI Ref ID J:86414)
    • decreased intestinal cholesterol absorption
      • mutants exhibit a significant decrease in the rate of cholesterol absorption as well as the amount of cholesterol absorbed from a single meal   (MGI Ref ID J:86414)
      • majority of fat absorption occurs in the distal intestinal segments instead of the proximal intestinal segments as in wild-type, with a significant level occurring in the terminal ileum   (MGI Ref ID J:86414)
      • intestinal uptake of cholesterol is significantly decreased in segments 1 and 2 of the intestine but no changes in the distal portions of the intestine when compared with wild-type mice   (MGI Ref ID J:86414)
  • homeostasis/metabolism phenotype
  • abnormal bile salt homeostasis
    • mutants exhibit a difference in the composition of minor bile acids, with a decrease in the amount of taurochenodeoxycholate and an increase in taurodeoxycholate compared to wild-type, however no differences in the cholesterol/bile acid ratio   (MGI Ref ID J:86414)
  • abnormal intestinal lipid absorption
    • mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption   (MGI Ref ID J:86414)
    • decreased intestinal cholesterol absorption
      • mutants exhibit a significant decrease in the rate of cholesterol absorption as well as the amount of cholesterol absorbed from a single meal   (MGI Ref ID J:86414)
      • majority of fat absorption occurs in the distal intestinal segments instead of the proximal intestinal segments as in wild-type, with a significant level occurring in the terminal ileum   (MGI Ref ID J:86414)
      • intestinal uptake of cholesterol is significantly decreased in segments 1 and 2 of the intestine but no changes in the distal portions of the intestine when compared with wild-type mice   (MGI Ref ID J:86414)

Pnliptm1Dyh/Pnliptm1Dyh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • homeostasis/metabolism phenotype
  • abnormal intestinal lipid absorption
    • triglyceride absorption is reduced (80.1+/- 3.6%) compared to wild-type (91.5 +/- 0.7%) mice when fed a Western-style diet (high fat)   (MGI Ref ID J:124658)
    • using a [14]C]tripalmitin tracer to determine the levels of triglycerides, long chain retinyl esters and cholesterol absorption, mice have 47% less [14]C] than in wild-type mice after 9 hours   (MGI Ref ID J:124658)
    • using [3]retinyl palmitate mixed in olive oil or in low fat chow, the rate and amount of retinyl ester absorption is reduced   (MGI Ref ID J:124658)
    • however, absorption of cholesteryl ester is normal   (MGI Ref ID J:124658)
    • decreased intestinal cholesterol absorption
      • when fed a high fat diet, cholesterol absorption is decreased   (MGI Ref ID J:124658)
  • decreased circulating cholesterol level
    • when fed a high fat diet, plasma cholesterol levels are 36% less than in wild-type mice fed a high fat diet   (MGI Ref ID J:124658)
  • decreased circulating insulin level
    • when fed a high fat diet, fasting insulin levels are lower than in similarly treated wild-type mice   (MGI Ref ID J:124658)
  • decreased susceptibility to diet-induced obesity
    • mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet   (MGI Ref ID J:124658)
  • insulin resistance
    • mice are more insulin resistant than wild-type mice and Celtm1Dyh homozygotes   (MGI Ref ID J:124658)
  • liver/biliary system phenotype
  • decreased liver weight
    • liver weight gain associated with consuming a high fat diet is reduced compared to in similarly treated wild-type mice   (MGI Ref ID J:124658)
  • growth/size/body phenotype
  • decreased percent body fat
    • at 25 weeks of age, mice on a high fat diet have 6.5% less body fat mass than wild-type mice   (MGI Ref ID J:124658)
  • decreased susceptibility to diet-induced obesity
    • mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet   (MGI Ref ID J:124658)
  • increased lean body mass
    • at 25 weeks of age, mice on a high fat diet have 6.7% more lean body mass than wild-type mice   (MGI Ref ID J:124658)
  • adipose tissue phenotype
  • decreased percent body fat
    • at 25 weeks of age, mice on a high fat diet have 6.5% less body fat mass than wild-type mice   (MGI Ref ID J:124658)
  • digestive/alimentary phenotype
  • abnormal intestinal lipid absorption
    • triglyceride absorption is reduced (80.1+/- 3.6%) compared to wild-type (91.5 +/- 0.7%) mice when fed a Western-style diet (high fat)   (MGI Ref ID J:124658)
    • using a [14]C]tripalmitin tracer to determine the levels of triglycerides, long chain retinyl esters and cholesterol absorption, mice have 47% less [14]C] than in wild-type mice after 9 hours   (MGI Ref ID J:124658)
    • using [3]retinyl palmitate mixed in olive oil or in low fat chow, the rate and amount of retinyl ester absorption is reduced   (MGI Ref ID J:124658)
    • however, absorption of cholesteryl ester is normal   (MGI Ref ID J:124658)
    • decreased intestinal cholesterol absorption
      • when fed a high fat diet, cholesterol absorption is decreased   (MGI Ref ID J:124658)
View Research Applications

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

Cardiovascular Research
Hypertriglyceridemia
Hypotriglyceridemia
Other
      altered fat metabolism
      altered lipoprotein profile

Endocrine Deficiency Research
Gastrointestinal Defects
Pancreas Defects

Internal/Organ Research
Gastrointestinal Defects

Metabolism Research
Enzyme Deficiency
      exocrine pancreatic insufficiency
Lipid Metabolism

Research Tools
Cardiovascular Research
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pnliptm1Dyh
Allele Name targeted mutation 1, David Y Hui
Allele Type Targeted (Null/Knockout)
Common Name(s) PTL-;
Mutation Made By David Hui,   University of Cincinnati - GRI
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<+>
Gene Symbol and Name Pnlip, pancreatic lipase
Chromosome 19
Gene Common Name(s) 1810007A24Rik; MGC:74173; PANLI; PL; PNLIPD; PTL; RIKEN cDNA 1810007A24 gene; pancreatic triglyceride lipase;
Molecular Note Exon 4 was disrupted by a neomycin selection cassette inserted by homologous recombination. The targeted exon has been reported to be essential for enzymatic activity. Protein was undetected in homozygous mutant mice by Western blot analysis of pancreatic extracts. Triglyceride hydrolysis was reduced by approximately 90% in homozygous mutanat mice. [MGI Ref ID J:86414]

Genotyping

Genotyping Information

Genotyping Protocols

Pnliptm1Dyh STD PCR, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Huggins KW; Camarota LM; Howles PN; Hui DY. 2003. Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice. J Biol Chem 278(44):42899-905. [PubMed: 12915407]  [MGI Ref ID J:86414]

Additional References

Pnliptm1Dyh related

Gilham D; Labonte ED; Rojas JC; Jandacek RJ; Howles PN; Hui DY. 2007. Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice. J Biol Chem 282(34):24642-9. [PubMed: 17604277]  [MGI Ref ID J:124658]

Sproule TJ; Bubier JA; Grandi FC; Sun VZ; Philip VM; McPhee CG; Adkins EB; Sundberg JP; Roopenian DC. 2014. Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice. PLoS Genet 10(2):e1004068. [PubMed: 24550734]  [MGI Ref ID J:211010]

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* $2140.00
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 will fulfill 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* $2782.00
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 will fulfill 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
 
  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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