Pctp<tm1Bor> Targeted Allele Detail MGI Mouse (MGI:2673156)

Pctp^tm1Bor
Targeted Allele Detail

Nomenclature

Symbol:	Pctp^tm1Bor
Name:	phosphatidylcholine transfer protein; targeted mutation 1, Piet Borst
MGI ID:	MGI:2673156
Synonyms:	Pc-tp -, Pctp^-
Gene:	Pctp Location: Chr11:89843979-89864208 bp, - strand Genetic Position: Chr11, 52.0 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:57946
Parent Cell Line:	E14 (ES Cell)
Strain of Origin:	129P2/OlaHsd

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	A neomycin selection gene replaced exons C and D by homologous recombination. Western blot analysis demonstrated that no detectable protein product was made in the cytosol of cells derived from homozygous mice. (J:57946)

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 Pctp Mutation:	4 strains or lines 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	hm3	hm4
cellular		√
increased apoptosis		√
		hm1	hm2	hm3	hm4
homeostasis/metabolism			√		√
abnormal bile salt level			√		√
abnormal phospholipid level			√
decreased cholesterol level					√
increased cholesterol level					√
		hm1	hm2	hm3	hm4
immune system		√
abnormal macrophage physiology		√
		hm1	hm2	hm3	hm4
liver/biliary system			√		√
abnormal bile canaliculus morphology			√		√
abnormal gall bladder physiology			√		√
abnormal bile composition			√
gallstones			√
abnormal bile secretion					√
		hm1	hm2	hm3	hm4
normal phenotype				N
no abnormal phenotype detected				N

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Pctp^tm1Bor/Pctp^tm1Bor	B6.129P2-Pctp^tm1Bor
cellular increased apoptosis (J:115284) macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages immune system abnormal macrophage physiology (J:115284) macrophages loaded with cholesteryl esters show impaired apoAI-mediated efflux of phospholipids and cholesterol compared to wild-type macrophages macrophages loaded with free (unesterified) cholesterol (FC) show significantly more apoptotic cell death and total cell death compared to FC-loaded wild-type macrophages
Genotype	Allelic Composition	Genetic Background
hm2	Pctp^tm1Bor/Pctp^tm1Bor	involves: 129P2/OlaHsd * C57BL/6J
liver/biliary system abnormal bile canaliculus morphology (J:115285) in mutant livers, bile canaliculi show extensive branching at membrane surface abnormal gall bladder physiology (J:115285) Background Sensitivity: occlusion of gall bladder with mucin occurs at 7 days on a lithogenic diet compared to 18 hours on the FVB/NJ background abnormal bile composition (J:115285) Background Sensitivity: phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates Background Sensitivity: on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile Background Sensitivity: on a lithogenic diet, after 7 days, mice have 1.3 fold lower biliary cholesterol levels in bile compared to wild-type littermates gallstones (J:115285) Background Sensitivity: on a lithogenic diet, abundant liquid and solid cholesterol crystals that precede formation of macroscopic cholesterol gallstones are observed after 9 days homeostasis/metabolism abnormal bile salt level (J:115285) Background Sensitivity: relative concentration of tauromuricholate (TMC) is reduced and tauroursdeoxycholate (TUDC) and taurocholate (TC) concentrations are increased compared to control Background Sensitivity: bile salt concentrations are 1.3 fold lower than controls on lithogenic diets compared to mutants on the FVB/NJ background on a lithogenic diet, TUDC concentration increases in mutants and controls, but remain higher in mutants; TC remains unchanged in mutants but increases in wild-type abnormal phospholipid level (J:115285) phospholipids in bile of mice on a chow diet are 1.3 fold higher than littermates on a lithogenic diet, after 7 days, mice have 1.3 fold lower phospholipid levels in bile
Genotype	Allelic Composition	Genetic Background
hm3	Pctp^tm1Bor/Pctp^tm1Bor	involves: 129P2/OlaHsd * FVB
normal phenotype no abnormal phenotype detected (J:57946) mice do not exhibit defects in lipid metabolism, liver function or lung surfactant production
Genotype	Allelic Composition	Genetic Background
hm4	Pctp^tm1Bor/Pctp^tm1Bor	involves: 129P2/OlaHsd * FVB/NJ
liver/biliary system abnormal bile canaliculus morphology (J:115285) in mutant livers, bile canaliculi show extensive branching at membrane surface bile canaliculi and junctional complexes appear more tortuous abnormal gall bladder physiology (J:115285) Background Sensitivity: occlusion of gall bladder with mucin occurs at 18 hours on a lithogenic diet Background Sensitivity: occlusion occurs much more quickly than on the C57BL/6J background abnormal bile secretion (J:115285) bile flow rate is reduced by ~35% after 30 minutes in mutants on a regular chow diet homeostasis/metabolism abnormal bile salt level (J:115285) Background Sensitivity: bile salt concentrations are 4.3 fold higher than controls on regular chow diets Background Sensitivity: there is marked increase in bile salt secretion on chow diet Background Sensitivity: on lithogenic diet, concentration decreases; in wild-type, concentrations increase such that both genotypes have similar bile salt concentrations Background Sensitivity: on a chow diet, TC concentration is higher than controls, while other bile salt concentrations are reduced; on a lithogenic diet, percentage of TUDC is higher in mutants, but other types are similar in both mutants and controls decreased cholesterol level (J:115285) Background Sensitivity: on a lithogenic diet, biliary cholesterol levels decrease, but levels increase in wild-type increased cholesterol level (J:115285) Background Sensitivity: in chow-fed mice, biliary cholesterol levels are 5.9 fold higher than in controls

References

Original:	J:57946 van Helvoort A et al., "Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces." Proc Natl Acad Sci U S A 1999 Sep 28;96(20):11501-6
All:	7 reference(s)

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