Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Heterozygote         (Female x Male)   30-SEP-09 Species laboratory mouse Generation N16+N1F (29-SEP-09)   Donating Investigator David 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
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Pnlip^tm1Dyh/Pnlip^tm1Dyh

        B6.129-Pnlip^tm1Dyh

• digestive/alimentary phenotype
• abnormal feces composition (MGI Ref ID J:86414)
  • 45% decrease in the amount of cholesterol in feces collected over a 24 hour period, indicating decreased absorption of cholesterol through the intestine
• abnormal lipid absorption (MGI Ref ID J:86414)
  • mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption
• decreased cholesterol absorption (MGI Ref ID J:86414)
  • mutants exhibit a significant decrease in the rate of cholesterol absorption as well as the amount of cholesterol absorbed from a single meal
  • 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
  • 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
• homeostasis/metabolism phenotype
• abnormal bile salt homeostasis (MGI Ref ID J:86414)
  • 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
• abnormal lipid absorption (MGI Ref ID J:86414)
  • mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption
• decreased cholesterol absorption (MGI Ref ID J:86414)
  • mutants exhibit a significant decrease in the rate of cholesterol absorption as well as the amount of cholesterol absorbed from a single meal
  • 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
  • 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

Pnlip^tm1Dyh/Pnlip^tm1Dyh

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• homeostasis/metabolism phenotype
• abnormal lipid absorption (MGI Ref ID J:124658)
  • 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)
  • 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
  • using [³]retinyl palmitate mixed in olive oil or in low fat chow, the rate and amount of retinyl ester absorption is reduced
  • however, absorption of cholesteryl ester is normal
• decreased cholesterol absorption (MGI Ref ID J:124658)
  • when fed a high fat diet, cholesterol absorption is decreased
• decreased circulating cholesterol level (MGI Ref ID J:124658)
  • when fed a high fat diet, plasma cholesterol levels are 36% less than in wild-type mice fed a high fat diet
• decreased circulating insulin level (MGI Ref ID J:124658)
  • when fed a high fat diet, fasting insulin levels are lower than in similarly treated wild-type mice
• increased resistance to diet-induced obesity (MGI Ref ID J:124658)
  • mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet
• insulin resistance (MGI Ref ID J:124658)
  • mice are more insulin resistant than wild-type mice and Cel^tm1Dyh homozygotes
• liver/biliary system phenotype
• decreased liver weight (MGI Ref ID J:124658)
  • liver weight gain associated with consuming a high fat diet is reduced compared to in similarly treated wild-type mice
• growth/size phenotype
• increased lean body mass (MGI Ref ID J:124658)
  • at 25 weeks of age, mice on a high fat diet have 6.7% more lean body mass than wild-type mice
• increased resistance to diet-induced obesity (MGI Ref ID J:124658)
  • mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet
• adipose tissue phenotype
• decreased percent body fat (MGI Ref ID J:124658)
  • at 25 weeks of age, mice on a high fat diet have 6.5% less body fat mass than wild-type mice
• digestive/alimentary phenotype
• abnormal lipid absorption (MGI Ref ID J:124658)
  • 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)
  • 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
  • using [³]retinyl palmitate mixed in olive oil or in low fat chow, the rate and amount of retinyl ester absorption is reduced
  • however, absorption of cholesteryl ester is normal
• decreased cholesterol absorption (MGI Ref ID J:124658)
  • when fed a high fat diet, cholesterol absorption is decreased

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

Allele Symbol		Pnliptm1Dyh
Allele Name		targeted mutation 1, David Y Hui
Allele Type		Targeted (knock-out)
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 Name		R1
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; 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

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Genotyping resources and troubleshooting

References

References

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

Pnlip^tm1Dyh 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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   30-SEP-09

Purchasing information

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

 

This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date: 09-NOV-09

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Pricing

Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
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'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.

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