Pnlip<tm1Dyh> Targeted Allele Detail MGI Mouse (MGI:2681122)

Pnlip^tm1Dyh
Targeted Allele Detail

Nomenclature

Symbol:	Pnlip^tm1Dyh
Name:	pancreatic lipase; targeted mutation 1, David Y Hui
MGI ID:	MGI:2681122
Synonyms:	PTL^-/-
Gene:	Pnlip Location: Chr19:58744855-58756276 bp, + strand Genetic Position: Chr19, 29.0 cM, cytoband D3

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:86414
Parent Cell Line:	R1 (ES Cell)
Strain of Origin:	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺

Mutation
description

Allele Type:	Targeted (knock-out)
Mutation:	Disruption caused by insertion of vector
	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. (J:86414)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Pnlip Mutation:	1 strain or line available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	cx3
adipose tissue			√	√
decreased percent body fat			√	√
		hm1	hm2	cx3
digestive/alimentary system		√	√	√
abnormal feces composition		√
abnormal lipid absorption		√	√	√
decreased cholesterol absorption		√	√	√
		hm1	hm2	cx3
growth/size			√	√
increased resistance to diet-induced obesity			√	√
increased lean body mass			√	√
		hm1	hm2	cx3
homeostasis/metabolism		√	√	√
abnormal lipid absorption		√	√	√
decreased cholesterol absorption		√	√	√
abnormal bile salt homeostasis		√
increased resistance to diet-induced obesity			√	√
decreased circulating insulin level			√	√
decreased circulating cholesterol level			√	√
insulin resistance			√	√
		hm1	hm2	cx3
liver/biliary system			√	√
decreased liver weight			√	√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Pnlip^tm1Dyh/Pnlip^tm1Dyh	B6.129-Pnlip^tm1Dyh
digestive/alimentary system abnormal feces composition (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 (J:86414) mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption decreased cholesterol absorption (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 abnormal lipid absorption (J:86414) mutants exhibit delayed triglyceride absorption after feeding but no difference in overall fat absorption decreased cholesterol absorption (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 abnormal bile salt homeostasis (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
Genotype	Allelic Composition	Genetic Background
hm2	Pnlip^tm1Dyh/Pnlip^tm1Dyh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6
homeostasis/metabolism abnormal lipid absorption (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 (J:124658) when fed a high fat diet, cholesterol absorption is decreased increased resistance to diet-induced obesity (J:124658) mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet decreased circulating insulin level (J:124658) when fed a high fat diet, fasting insulin levels are lower than in similarly treated wild-type mice decreased circulating cholesterol level (J:124658) when fed a high fat diet, plasma cholesterol levels are 36% less than in wild-type mice fed a high fat diet insulin resistance (J:124658) mice are more insulin resistant than wild-type mice and Cel^tm1Dyh homozygotes liver/biliary system decreased liver weight (J:124658) liver weight gain associated with consuming a high fat diet is reduced compared to in similarly treated wild-type mice growth/size increased resistance to diet-induced obesity (J:124658) mice weight less than wild-type counterparts after 10.5 weeks on a high fat diet increased lean body mass (J:124658) at 25 weeks of age, mice on a high fat diet have 6.7% more lean body mass than wild-type mice adipose tissue decreased percent body fat (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 system abnormal lipid absorption (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 (J:124658) when fed a high fat diet, cholesterol absorption is decreased
Genotype	Allelic Composition	Genetic Background
cx3	Cel^tm1Dyh/Cel^tm1Dyh Pnlip^tm1Dyh/Pnlip^tm1Dyh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6
homeostasis/metabolism abnormal lipid absorption (J:124658) triglyceride absorption is dramatically reduced (60.1+/- 3.8%) compared to wild-type (91.5 +/- 0.7%) mice and in Pnlip^tm1Dyh homozygotes (80.1+/- 3.6%) 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 52% 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 to a greater extent than in Pnlip^tm1Dyh homozygotes using [¹⁴C]cholesteryl oleate, absorption of cholesteryl ester is nearly eliminated as in Cel^tm1Dyh homozygotes decreased cholesterol absorption (J:124658) when fed a high fat diet, cholesterol absorption is decreased similar to in Pnlip^tm1Dyh homozygotes increased resistance to diet-induced obesity (J:124658) mice weight less than wild-type counterparts after 0.5 weeks on a high fat diet decreased circulating insulin level (J:124658) when fed a high fat diet, fasting insulin levels are lower than in similarly treated wild-type mice decreased circulating cholesterol level (J:124658) when fed a high fat diet, plasma cholesterol levels are 45% less than in wild-type mice fed a high fat diet insulin resistance (J:124658) mice are more insulin resistant than wild-type mice and Cel^tm1Dyh homozygotes liver/biliary system decreased liver weight (J:124658) liver weight gain associated with consuming a high fat diet is reduced compared to in similarly treated wild-type mice growth/size increased resistance to diet-induced obesity (J:124658) mice weight less than wild-type counterparts after 0.5 weeks on a high fat diet increased lean body mass (J:124658) at 25 weeks of age, mice on a high fat diet have 12.3% more lean body mass than wild-type mice adipose tissue decreased percent body fat (J:124658) at 25 weeks of age, mice on a high fat diet have 12.5% less body fat mass than wild-type mice digestive/alimentary system abnormal lipid absorption (J:124658) triglyceride absorption is dramatically reduced (60.1+/- 3.8%) compared to wild-type (91.5 +/- 0.7%) mice and in Pnlip^tm1Dyh homozygotes (80.1+/- 3.6%) 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 52% 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 to a greater extent than in Pnlip^tm1Dyh homozygotes using [¹⁴C]cholesteryl oleate, absorption of cholesteryl ester is nearly eliminated as in Cel^tm1Dyh homozygotes decreased cholesterol absorption (J:124658) when fed a high fat diet, cholesterol absorption is decreased similar to in Pnlip^tm1Dyh homozygotes

References

Original:	J:86414 Huggins KW et al., "Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice." J Biol Chem 2003 Oct 31;278(44):42899-905
All:	2 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources Funding Information Warranty Disclaimer & Copyright Notice Send questions and comments to User Support.	last database update 11/20/2009 MGI_4.31 Web browser compatibility