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.
David Y Hui, University of Cincinnati - GRI
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.
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.
|Allele Name||targeted mutation 1, David Y Hui|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pnlip, pancreatic lipase|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|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.|
|Mutations Made By|| |
David Hui, University of Cincinnati - GRI
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129(Cg)-Pnliptm1Dyh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008884 in your Materials and Methods section.