Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Xian-cheng Jiang, Columbia University
Mice that are homozygous null for the Pltp gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Pltp mRNA is detected in the tissues that normally express Pltp (lung and liver). No plasma Pltp activity is detected. Marked decreases in plasma HDL phospholipid (66%), cholesteryl ester (69%), free cholesterol (70%) and apoAI are observed. When mice are maintained on a high fat/high cholesterol diet, similar reductions are observed, as are increases in VLDL and LDL phospholipid, free cholesterol and cholesteryl ester. This mutant strain offers a model useful in studies related to cholesterol metabolism and atherosclerosis.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the Pltp gene encoding intron 1, exon 2 and a portion of intron 2. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6 females.
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
- reproductive system phenotype
- *normal* reproductive system phenotype
- normal testis morphology with no apparent spermatogenic defects (MGI Ref ID J:107906)
- normal weights of testis, epididymis, prostate, vesicular, and coagulating glands (MGI Ref ID J:107906)
- normal testicular and plasma testosterone levels (MGI Ref ID J:107906)
- normal sperm concentration, viability and morphology (MGI Ref ID J:107906)
- abnormal caput epididymis morphology
- mutant caput shows a 26% reduction in alpha-tocopherol concentration relative to wild-type (MGI Ref ID J:107906)
- abnormal cauda epididymis morphology
- mutant cauda shows a 21% reduction in alpha-tocopherol concentration relative to wild-type (MGI Ref ID J:107906)
- abnormal sperm physiology
- mutant spermatozoa show a significant reduction in alpha-tocopherol content relative to wild-type spermatozoa (caput: -29%, cauda: -26%), indicating vitamin E deficiency (MGI Ref ID J:107906)
- impaired fertilization
- in vitro fertilization rates of wild-type oocytes with mutant spermatozoa are reduced by 60% relative to those measured with spermatozoa from wild-type males (MGI Ref ID J:107906)
- reduced male fertility
- when male homozygotes are crossed with wild-type females, the total number of pups produced over a 2-month mating period is reduced by 31% (MGI Ref ID J:107906)
- homeostasis/metabolism phenotype
- abnormal circulating cholesterol level (MGI Ref ID J:53521)
- decreased circulating HDL cholesterol level
- HDL cholesteryl ester and free cholesterol are markedly reduced (MGI Ref ID J:53521)
- increased circulating LDL cholesterol level
- relative to controls on a high fat diet (MGI Ref ID J:53521)
- increased circulating VLDL cholesterol level
- relative to controls on a high fat diet (MGI Ref ID J:53521)
- abnormal phospholipid level
- abnormal vitamin E level
- alpha-tocopherol, the main vitamin E isomer in vivo, is significantly less abundant in the spermatoza and epididymis of homozygous mutant male mice (MGI Ref ID J:107906)
- vision/eye phenotype
- abnormal cornea morphology
- corneas exhibit detaching apical cells more frequently than in wild-type corneas (MGI Ref ID J:171592)
- 2.4% of mice exhibit spontaneous corneal perforations with stromal damage, infiltration of lymphocytes to the ulcus area and disorganization and thickening of the adjacent epithelia (MGI Ref ID J:171592)
- abnormal corneal epithelium morphology
- mutants with corneal perforations exhibit a disorganized and thickened epithelium (MGI Ref ID J:171592)
- mutants exhibit an increase in corneal epithelial permeability to carboxyfluorescein, a characteristic of dry eye (MGI Ref ID J:171592)
- mutants have decreased expression of the tight junction protein occludin in the corneal epithelium (MGI Ref ID J:171592)
- abnormal corneal stroma morphology
- mutants with corneal perforations exhibit stromal damage (MGI Ref ID J:171592)
- dry eyes
- mutants show characteristics of dry eye syndrome, with morphologic changes in corneal epithelium, increased corneal permeability to carboxyfluorescein, and cleavage of corneal epithelium occludin, however tear fluid production is similar to wild-type and eyelid and meibomian gland morphologies are normal (MGI Ref ID J:171592)View Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
|Allele Name||targeted mutation 1, Xian-cheng Jiang|
|Allele Type||Targeted (Null/Knockout)|
|Mutation Made By||Xian-cheng Jiang, Columbia University|
|Gene Symbol and Name||Pltp, phospholipid transfer protein|
|Gene Common Name(s)||BPIFE; HDLCQ9; OD107;|
|General Note||Phenotypic Similarity to Human Syndrome: Dry Eye Syndrome (J:171592).|
|Molecular Note||A neomycin selection cassette replaced a genomic fragment containing exon 2, which encodes the initiation codon, the signal peptide and the first 16 amino acids of the mature protein. Northern blot and RNase protection analysis on RNA derived from lung of homozygous mice demonstrated that no detectable transcript was produced from this allele. Activity assays on plasma of homozygous mice confirmed that no functional protein was expressed from this allele. [MGI Ref ID J:53521]|
Jiang XC; Bruce C; Mar J; Lin M; Ji Y; Francone OL; Tall AR. 1999. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest 103(6):907-14. [PubMed: 10079112] [MGI Ref ID J:53521]
Desrumaux C; Deckert V; Lemaire-Ewing S; Mossiat C; Athias A; Vandroux D; Dumont L; Monier S; Pais de Barros JP; Klein A; De Maistre E; Blache D; Beley A; Marie C; Garnier P; Lagrost L. 2010. Plasma phospholipid transfer protein deficiency in mice is associated with a reduced thrombotic response to acute intravascular oxidative stress. Arterioscler Thromb Vasc Biol 30(12):2452-7. [PubMed: 20864671] [MGI Ref ID J:183145]
Desrumaux C; Risold PY; Schroeder H; Deckert V; Masson D; Athias A; Laplanche H; Le Guern N; Blache D; Jiang XC; Tall AR; Desor D; Lagrost L. 2005. Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content and increases anxiety in mice. FASEB J 19(2):296-7. [PubMed: 15576481] [MGI Ref ID J:105096]
Drouineaud V; Lagrost L; Klein A; Desrumaux C; Le Guern N; Athias A; Menetrier F; Moiroux P; Sagot P; Jimenez C; Masson D; Deckert V. 2006. Phospholipid transfer protein deficiency reduces sperm motility and impairs fertility of mouse males. FASEB J 20(6):794-6. [PubMed: 16467369] [MGI Ref ID J:107906]
Gautier T; Klein A; Deckert V; Desrumaux C; Ogier N; Sberna AL; Paul C; Le Guern N; Athias A; Montange T; Monier S; Piard F; Jiang XC; Masson D; Lagrost L. 2008. Effect of plasma phospholipid transfer protein deficiency on lethal endotoxemia in mice. J Biol Chem 283(27):18702-10. [PubMed: 18458077] [MGI Ref ID J:138121]
Jiang XC; Li Z; Liu R; Yang XP; Pan M; Lagrost L; Fisher EA; Williams KJ. 2005. Phospholipid transfer protein deficiency impairs apolipoprotein-B secretion from hepatocytes by stimulating a proteolytic pathway through a relative deficiency of vitamin E and an increase in intracellular oxidants. J Biol Chem 280(18):18336-40. [PubMed: 15734742] [MGI Ref ID J:99065]
Jiang XC; Qin S; Qiao C; Kawano K; Lin M; Skold A; Xiao X; Tall AR. 2001. Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7(7):847-52. [PubMed: 11433351] [MGI Ref ID J:70250]
Jiang XC; Tall AR; Qin S; Lin M; Schneider M; Lalanne F; Deckert V; Desrumaux C; Athias A; Witztum JL; Lagrost L. 2002. Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. J Biol Chem 277(35):31850-6. [PubMed: 12105225] [MGI Ref ID J:120468]
Kawano K; Qin S; Vieu C; Collet X; Jiang XC. 2002. Role of hepatic lipase and scavenger receptor BI in clearing phospholipid/free cholesterol-rich lipoproteins in PLTP-deficient mice. Biochim Biophys Acta 1583(2):133-40. [PubMed: 12117557] [MGI Ref ID J:115519]
Kawano K; Qin SC; Lin M; Tall AR; Jiang Xc. 2000. Cholesteryl ester transfer protein and phospholipid transfer protein have nonoverlapping functions in vivo J Biol Chem 275(38):29477-81. [PubMed: 10893412] [MGI Ref ID J:64848]
Klein A; Deckert V; Schneider M; Dutrillaux F; Hammann A; Athias A; Le Guern N; Pais de Barros JP; Desrumaux C; Masson D; Jiang XC; Lagrost L. 2006. Alpha-tocopherol modulates phosphatidylserine externalization in erythrocytes: relevance in phospholipid transfer protein-deficient mice. Arterioscler Thromb Vasc Biol 26(9):2160-7. [PubMed: 16825594] [MGI Ref ID J:127991]
Lee-Rueckert M; Vikstedt R; Metso J; Ehnholm C; Kovanen PT; Jauhiainen M. 2006. Absence of endogenous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells. J Lipid Res 47(8):1725-32. [PubMed: 16687660] [MGI Ref ID J:112586]
Liu R; Iqbal J; Yeang C; Wang DQ; Hussain MM; Jiang XC. 2007. Phospholipid transfer protein-deficient mice absorb less cholesterol. Arterioscler Thromb Vasc Biol 27(9):2014-21. [PubMed: 17641249] [MGI Ref ID J:134894]
Nguyen AT; Mandard S; Dray C; Deckert V; Valet P; Besnard P; Drucker DJ; Lagrost L; Grober J. 2014. Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway. Diabetes 63(2):471-82. [PubMed: 24186868] [MGI Ref ID J:209002]
Ogier N; Klein A; Deckert V; Athias A; Bessede G; Le Guern N; Lagrost L; Desrumaux C. 2007. Cholesterol accumulation is increased in macrophages of phospholipid transfer protein-deficient mice: normalization by dietary alpha-tocopherol supplementation. Arterioscler Thromb Vasc Biol 27(11):2407-12. [PubMed: 17717294] [MGI Ref ID J:134876]
Qin S; Kawano K; Bruce C; Lin M; Bisgaier C; Tall AR; Jiang X. 2000. Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins. J Lipid Res 41(2):269-76. [PubMed: 10681411] [MGI Ref ID J:60580]
Samyn H; Moerland M; van Gent T; van Haperen R; van Tol A; de Crom R. 2009. Reduction of HDL levels lowers plasma PLTP and affects its distribution among lipoproteins in mice. Biochim Biophys Acta 1791(8):790-6. [PubMed: 19422933] [MGI Ref ID J:153479]
Schlitt A; Liu J; Yan D; Mondragon-Escorpizo M; Norin AJ; Jiang XC. 2005. Anti-inflammatory effects of phospholipid transfer protein (PLTP) deficiency in mice. Biochim Biophys Acta 1733(2-3):187-91. [PubMed: 15863365] [MGI Ref ID J:99061]
Setala NL; Metso J; Jauhiainen M; Sajantila A; Holopainen JM. 2011. Dry Eye Symptoms Are Increased in Mice Deficient in Phospholipid Transfer Protein (PLTP). Am J Pathol 178(5):2058-65. [PubMed: 21514421] [MGI Ref ID J:171592]
Shelly L; Royer L; Sand T; Jensen H; Luo Y. 2008. Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice. J Lipid Res 49(4):773-81. [PubMed: 18198166] [MGI Ref ID J:133585]
Valenta DT; Bulgrien JJ; Bonnet DJ; Curtiss LK. 2008. Macrophage PLTP is atheroprotective in LDLr-deficient mice with systemic PLTP deficiency. J Lipid Res 49(1):24-32. [PubMed: 17928634] [MGI Ref ID J:130081]
Vikstedt R; Ye D; Metso J; Hildebrand RB; Van Berkel TJ; Ehnholm C; Jauhiainen M; Van Eck M. 2007. Macrophage phospholipid transfer protein contributes significantly to total plasma phospholipid transfer activity and its deficiency leads to diminished atherosclerotic lesion development. Arterioscler Thromb Vasc Biol 27(3):578-86. [PubMed: 17170377] [MGI Ref ID J:148673]
Webb NR; de Beer MC; Asztalos BF; Whitaker N; van der Westhuyzen DR; de Beer FC. 2004. Remodeling of HDL remnants generated by scavenger receptor class B type I. J Lipid Res 45(9):1666-73. [PubMed: 15210842] [MGI Ref ID J:93254]
Yan D; Navab M; Bruce C; Fogelman AM; Jiang XC. 2004. PLTP deficiency improves the anti-inflammatory properties of HDL and reduces the ability of LDL to induce monocyte chemotactic activity. J Lipid Res 45(10):1852-8. [PubMed: 15258196] [MGI Ref ID J:93620]
Yeang C; Qin S; Chen K; Wang DQ; Jiang XC. 2010. Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism. J Lipid Res 51(10):2993-3002. [PubMed: 20543142] [MGI Ref ID J:165459]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6 for at least eight generations.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2525.00
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.
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 willfulfill 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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $3283.00
Cryorecovery - Standard.
Progeny testing is not required.
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