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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 Background Strain FVB/N Donor Strain 129P2 via E14TG2a ES cell line Generation N6F10pN1p (09-NOV-05) Donating Investigator Piet Borst, The Netherlands Cancer Institute Appearance
albino
Related Genotype: Tyrc/TyrcImportant Note
This strain is homozygous for the retinal degeneration allele Pde6brd1.Description
Mice homozygous for the Abcb4tm1Bor mutation lack the ability to secrete phospholipid into the bile from the liver. They develop a degenerative liver disease. Portal inflammation ensues at an early age followed by hepatocellular carcinoma development after the age of 1 year. Bile from heterozygous mice has half the level of phospholipid when compared to bile from homozygotes. No liver pathology has been shown in heterozygotes.
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying Pde6brd1 allele
View Strains carrying Pde6brd1 (74 strains)
Strains carrying other alleles of Pde6b
004297 B6.CXB1-Pde6brd10/J 005252 B6EiC3Sn.BLiA-Ts(1716)65Dn/DnJ 003647 B6EiC3Sn.BLiAF1 002802 C3.BLiA Pde6b+-Krd/J 001979 C3A.BLiA-Pde6b+.O20-Prph2Rd2/J 001912 C3A.BLiA-Pde6b+/J 003648 C3Sn.BLiA-Pde6b+/Dn 004766 C57BL/6J-Pde6brd1-2J/J 004828 FVB.129P2-Pde6b+ Tyrc-ch/AntJ 004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J View Strains carrying other alleles of Pde6b (10 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Abcb4tm1Bor/Abcb4tm1Bor
FVB.129P2-Abcb4tm1Bor/J
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype (MGI Ref ID J:100491)
- mice exhibit normal plasma levels of sitosterol and campesterol
- increased circulating alanine transaminase level (MGI Ref ID J:100491)
- increased circulating aspartate transaminase level (MGI Ref ID J:100491)
- liver/biliary system phenotype
- abnormal bile composition (MGI Ref ID J:100491)
- bile cholesterol levels are decreased compared to in wild-type mice
- digestive/alimentary phenotype
- abnormal feces composition (MGI Ref ID J:100491)
- fecal acidic sterol levels are decreased 30% compared to in wild-type mice
- however, fecal neutral sterol levels are normal
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Abcb4tm1Bor/Abcb4tm1Bor
either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)
- homeostasis/metabolism phenotype
- abnormal blood homeostasis (MGI Ref ID J:15531)
- serum is yellowish, suggesting liver damage
- abnormal circulating alanine transaminase level (MGI Ref ID J:15531)
- 5.8-fold increase in alanine transaminase level
- abnormal circulating alkaline phosphatase level (MGI Ref ID J:15531)
- 3-fold increase in serum alkaline phosphatase level
- abnormal circulating aspartate transaminase level (MGI Ref ID J:15531)
- 4-fold increase in aspartate transaminase level
- abnormal circulating bilirubin level (MGI Ref ID J:15531)
- 12-fold elevated bilirubin level; ~50% of this is conjugated
- immune system phenotype
- bile duct inflammation (MGI Ref ID J:15531)
- inflammation of bile ducts
- liver inflammation (MGI Ref ID J:15531)
- portal inflammation with mixed inflammatory infiltrate and slight fibrosis
- liver/biliary system phenotype
- abnormal bile canaliculus morphology (MGI Ref ID J:15531)
- prominent widening and increased tortuosity of bile canaliculi with loss of microvilli is present
- abnormal bile composition (MGI Ref ID J:15531)
- absence of phospholipid secretion in bile, lipid secretion is decreased and there is a 15-reduction in cholesterol secretion in bile
- glutathione secretion in bile is ~14% of wild-type
- chloride secretion is slightly, but significantly, elevated
- phospolipid to bile salt ratio is only ~41% of wild-type
- abnormal bile duct morphology (MGI Ref ID J:15531)
- portal expansion due to ductular proliferation is seen
- abnormal bile secretion (MGI Ref ID J:15531)
- abnormal hepatocyte morphology (MGI Ref ID J:15531)
- hepatocyte degeneration, irregular size with nuclear polymorphism and focal necrosis are observed, along with increased proliferation
- bile duct inflammation (MGI Ref ID J:15531)
- inflammation of bile ducts
- dilated bile duct (MGI Ref ID J:15531)
- larger bile ducts are dilated
- intrahepatic cholestasis (MGI Ref ID J:15531)
- modesrate liver damage with cholestatic properties (raised serum-conjugated bilirubin) is observed
- liver inflammation (MGI Ref ID J:15531)
- portal inflammation with mixed inflammatory infiltrate and slight fibrosis
- endocrine/exocrine gland phenotype
- abnormal bile duct morphology (MGI Ref ID J:15531)
- portal expansion due to ductular proliferation is seen
Abcb4tm1Bor/Abcb4tm1Bor
involves: 129P2/OlaHsd * FVB
- homeostasis/metabolism phenotype
- abnormal circulating enzyme level (MGI Ref ID J:114411)
- increased circulating alanine transaminase level (MGI Ref ID J:114411)
- increased circulating aspartate transaminase level (MGI Ref ID J:114411)
- abnormal lipid homeostasis (MGI Ref ID J:114411)
- decreased cholesterol absorption (MGI Ref ID J:114411)
- 40% reduction in absorption efficiency
- decreased circulating cholesterol level (MGI Ref ID J:114411)
- plasma levels reduced
- increased circulating bilirubin level (MGI Ref ID J:114411)
- digestive/alimentary phenotype
- decreased cholesterol absorption (MGI Ref ID J:114411)
- 40% reduction in absorption efficiency
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Abcb4tm1Bor relatedCancer Research
Increased Tumor Incidence
Hepatomas: hepatacellular carcinoma
Pde6brd1 relatedCancer Research
Toxicology
Internal/Organ Research
Liver Defects
Metabolism Research
Research Tools
Toxicology Research
Mouse/Human Gene Homologs
retinitis pigmentosa, autosomal recessive
Sensorineural Research
Retinal Degeneration
| Allele Symbol | Abcb4tm1Bor | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Piet Borst | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Pgy2tm1Bor; mdr2-; mdr2neo1; | ||
| Mutation Made By | Piet Borst, The Netherlands Cancer Institute | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Abcb4, ATP-binding cassette, sub-family B (MDR/TAP), member 4 | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | ABC21; GBD1; MDR2; MDR2/3; MDR3; P glycoprotein 2; PFIC-3; PGY3; Pgy-2; Pgy2; mdr-2; | ||
| Molecular Note | A neomycin selection cassette replaced a genomic fragment containing exons 1 and 2. The translation initiation site is in exon 2. RNase proteiction assays indicated that mutant truncated transcripts are produced from this allele that contain exons 3-6 or 4-6. [MGI Ref ID J:15531] | ||
| Allele Symbol | Pde6brd1 | ||
| Allele Name | retinal degeneration 1 | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | Pdebrd1; rd; rd-1; rd1; rodless retina; | ||
Genotyping Protocols
Abcb4tm1Bor, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Smit JJ; Schinkel AH; Oude Elferink RP; Groen AK; Wagenaar E; van Deemter L; Mol CA; Ottenhoff R; van der Lugt NM; van Roon MA; van der Valk MA; Offerhaus GJ; Berns AJ; Borst P. 1993. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75(3):451-62. [PubMed: 8106172] [MGI Ref ID J:15531]
Borst P; Schinkel AH. 1996. What have we learnt thus far from mice with disrupted P-glycoprotein genes? Eur J Cancer 32A(6):985-90. [PubMed: 8763339] [MGI Ref ID J:33581]
Fickert P; Fuchsbichler A; Wagner M; Zollner G; Kaser A; Tilg H; Krause R; Lammert F; Langner C; Zatloukal K; Marschall HU; Denk H; Trauner M. 2004. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 127(1):261-74. [PubMed: 15236191] [MGI Ref ID J:93576]
Abcb4tm1Bor relatedBorst P; Schinkel AH. 1996. What have we learnt thus far from mice with disrupted P-glycoprotein genes? Eur J Cancer 32A(6):985-90. [PubMed: 8763339] [MGI Ref ID J:33581]
De Vree JM; Ottenhoff R; Bosma PJ; Smith AJ; Aten J; Elferink RP. 2000. Correction of liver disease by hepatocyte transplantation in a mouse model of progressive familial intrahepatic cholestasis Gastroenterology 119(6):1720-30. [PubMed: 11113093] [MGI Ref ID J:66180]
Dekkers DW; Comfurius P; Schroit AJ; Bevers EM; Zwaal RF. 1998. Transbilayer movement of NBD-labeled phospholipids in red blood cell membranes: outward-directed transport by the multidrug resistance protein 1 (MRP1). Biochemistry 37(42):14833-7. [PubMed: 9778357] [MGI Ref ID J:51135]
Eisenbraun MD; Miller RA. 1999. mdr1a-encoded P-glycoprotein is not required for peripheral T cell proliferation, cytokine release, or cytotoxic effector function in mice. J Immunol 163(5):2621-7. [PubMed: 10453001] [MGI Ref ID J:57091]
Fickert P; Fuchsbichler A; Wagner M; Zollner G; Kaser A; Tilg H; Krause R; Lammert F; Langner C; Zatloukal K; Marschall HU; Denk H; Trauner M. 2004. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 127(1):261-74. [PubMed: 15236191] [MGI Ref ID J:93576]
Frijters CM; Tuijn CJ; Ottenhoff R; Zegers BN; Groen AK; Elferink RP. 1999. The role of different P-glycoproteins in hepatobiliary secretion of fluorescently labeled short-chain phospholipids. J Lipid Res 40(11):1950-8. [PubMed: 10552998] [MGI Ref ID J:119840]
Groen AK; Van Wijland MJ; Frederiks WM; Smit JJ; Schinkel AH; Oude Elferink RP. 1995. Regulation of protein secretion into bile: studies in mice with a disrupted mdr2 p-glycoprotein gene. Gastroenterology 109(6):1997-2006. [PubMed: 7498666] [MGI Ref ID J:30489]
Hulzebos CV; Voshol PJ; Wolters H; Kruit JK; Ottenhof R; Groen AK; Stellaard F; Verkade HJ; Kuipers F. 2005. Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice. Liver Int 25(3):604-12. [PubMed: 15910498] [MGI Ref ID J:110130]
Katzenellenbogen M; Mizrahi L; Pappo O; Klopstock N; Olam D; Barash H; Domany E; Galun E; Goldenberg D. 2007. Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice. Mol Cancer Ther 6(4):1283-91. [PubMed: 17431106] [MGI Ref ID J:133445]
Katzenellenbogen M; Mizrahi L; Pappo O; Klopstock N; Olam D; Jacob-Hirsch J; Amariglio N; Rechavi G; Domany E; Galun E; Goldenberg D. 2007. Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice. Mol Cancer Res 5(11):1159-70. [PubMed: 18025261] [MGI Ref ID J:131750]
Katzenellenbogen M; Pappo O; Barash H; Klopstock N; Mizrahi L; Olam D; Jacob-Hirsch J; Amariglio N; Rechavi G; Mitchell LA; Kohen R; Domany E; Galun E; Goldenberg D. 2006. Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice. Cancer Res 66(8):4001-10. [PubMed: 16618719] [MGI Ref ID J:108307]
Klopstock N; Katzenellenbogen M; Pappo O; Sklair-Levy M; Olam D; Mizrahi L; Potikha T; Galun E; Goldenberg D. 2009. HCV tumor promoting effect is dependent on host genetic background. PLoS ONE 4(4):e5025. [PubMed: 19340302] [MGI Ref ID J:148175]
Kok T; Wolters H; Bloks VW; Havinga R; Jansen PL; Staels B; Kuipers F. 2003. Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated fasting response in the mouse. Gastroenterology 124(1):160-71. [PubMed: 12512040] [MGI Ref ID J:81018]
Kruit JK; Plosch T; Havinga R; Boverhof R; Groot PH; Groen AK; Kuipers F. 2005. Increased fecal neutral sterol loss upon liver X receptor activation is independent of biliary sterol secretion in mice. Gastroenterology 128(1):147-56. [PubMed: 15633131] [MGI Ref ID J:95371]
Lammert F; Wang DQ; Hillebrandt S; Geier A; Fickert P; Trauner M; Matern S; Paigen B; Carey MC. 2004. Spontaneous cholecysto- and hepatolithiasis in Mdr2-/- mice: a model for low phospholipid-associated cholelithiasis. Hepatology 39(1):117-28. [PubMed: 14752830] [MGI Ref ID J:105357]
Langheim S; Yu L; von Bergmann K; Lutjohann D; Xu F; Hobbs HH; Cohen JC. 2005. ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile. J Lipid Res 46(8):1732-8. [PubMed: 15930516] [MGI Ref ID J:100491]
Li Z; Agellon LB; Allen TM; Umeda M; Jewell L; Mason A; Vance DE. 2006. The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metab 3(5):321-31. [PubMed: 16679290] [MGI Ref ID J:129649]
Li Z; Agellon LB; Vance DE. 2007. Choline redistribution during adaptation to choline deprivation. J Biol Chem 282(14):10283-9. [PubMed: 17283071] [MGI Ref ID J:121149]
Li Z; Agellon LB; Vance DE. 2005. Phosphatidylcholine homeostasis and liver failure. J Biol Chem 280(45):37798-802. [PubMed: 16144842] [MGI Ref ID J:102893]
Mann DA; Oakley F. 2005. NF-kappaB: a signal for cancer. J Hepatol 42(4):610-1. [PubMed: 15763352] [MGI Ref ID J:97853]
Mauad TH; van Nieuwkerk CM; Dingemans KP; Smit JJ; Schinkel AH; Notenboom RG; van den Bergh Weerman MA; Verkruisen RP; Groen AK; Oude Elferink RP; van der Valk MA; Borst P; Offerhaus GJ. 1994. Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis. Am J Pathol 145(5):1237-45. [PubMed: 7977654] [MGI Ref ID J:21232]
Minich DM; Voshol PJ; Havinga R; Stellaard F; Kuipers F; Vonk RJ; Verkade HJ. 1999. Biliary phospholipid secretion is not required for intestinal absorption and plasma status of linoleic acid in mice. Biochim Biophys Acta 1441(1):14-22. [PubMed: 10526224] [MGI Ref ID J:114159]
Mustacich DJ; Shields J; Horton RA; Brown MK; Reed DJ. 1998. Biliary secretion of alpha-tocopherol and the role of the mdr2 P-glycoprotein in rats and mice. Arch Biochem Biophys 350(2):183-92. [PubMed: 9473291] [MGI Ref ID J:45890]
Oude Elferink RP; Ottenhoff R; van Wijland M; Smit JJ; Schinkel AH; Groen AK. 1995. Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse. J Clin Invest 95(1):31-8. [PubMed: 7814632] [MGI Ref ID J:22312]
Patsenker E; Popov Y; Stickel F; Jonczyk A; Goodman SL; Schuppan D. 2008. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology 135(2):660-70. [PubMed: 18538673] [MGI Ref ID J:141794]
Pikarsky E; Porat RM; Stein I; Abramovitch R; Amit S; Kasem S; Gutkovich-Pyest E; Urieli-Shoval S; Galun E; Ben-Neriah Y. 2004. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431(7007):461-6. [PubMed: 15329734] [MGI Ref ID J:92668]
Plosch T; Bloks VW; Baller JF; Havinga R; Verkade HJ; Jansen PL; Kuipers F. 2002. Mdr P-glycoproteins are not essential for biliary excretion of the hydrophobic heme precursor protoporphyrin in a griseofulvin-induced mouse model of erythropoietic protoporphyria. Hepatology 35(2):299-306. [PubMed: 11826402] [MGI Ref ID J:105815]
Rawles LA; Acuna D; Erickson RP. 2007. The role of multiple drug resistance proteins in fetal and/or placental protection against teratogen-induced orofacial clefting. Mol Reprod Dev 74(11):1483-9. [PubMed: 17440929] [MGI Ref ID J:128360]
Smith AJ; de Vree JM; Ottenhoff R; Oude Elferink RP; Schinkel AH; Borst P. 1998. Hepatocyte-specific expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice. Hepatology 28(2):530-6. [PubMed: 9696021] [MGI Ref ID J:50317]
Uhr M; Tontsch A; Namendorf C; Ripke S; Lucae S; Ising M; Dose T; Ebinger M; Rosenhagen M; Kohli M; Kloiber S; Salyakina D; Bettecken T; Specht M; Putz B; Binder EB; Muller-Myhsok B; Holsboer F. 2008. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron 57(2):203-9. [PubMed: 18215618] [MGI Ref ID J:135234]
Van Nieuwkerk CM; Elferink RP; Groen AK; Ottenhoff R; Tytgat GN; Dingemans KP; Van Den Bergh Weerman MA; Offerhaus GJ. 1996. Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 111(1):165-71. [PubMed: 8698195] [MGI Ref ID J:34646]
Voshol PJ; Havinga R; Wolters H; Ottenhoff R; Princen HM; Oude Elferink RP; Groen AK; Kuipers F. 1998. Reduced plasma cholesterol and increased fecal sterol loss in multidrug resistance gene 2 P-glycoprotein-deficient mice. Gastroenterology 114(5):1024-34. [PubMed: 9558293] [MGI Ref ID J:47805]
Voshol PJ; Minich DM; Havinga R; Elferink RP; Verkade HJ; Groen AK; Kuipers F. 2000. Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice [see comments] Gastroenterology 118(1):173-82. [PubMed: 10611166] [MGI Ref ID J:59783]
Voshol PJ; Schwarz M; Rigotti A; Krieger M; Groen AK; Kuipers F. 2001. Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine. Biochem J 356(Pt 2):317-25. [PubMed: 11368757] [MGI Ref ID J:114411]
Werner A; Havinga R; Perton F; Kuipers F; Verkade HJ. 2006. Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice. Am J Physiol Gastrointest Liver Physiol 290(6):G1177-85. [PubMed: 16384875] [MGI Ref ID J:111087]
Werner A; Minich DM; Havinga R; Bloks V; Van Goor H; Kuipers F; Verkade HJ. 2002. Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation. Am J Physiol Gastrointest Liver Physiol 283(4):G900-8. [PubMed: 12223350] [MGI Ref ID J:108285]
van der Velde AE; Vrins CL; van den Oever K; Kunne C; Oude Elferink RP; Kuipers F; Groen AK. 2007. Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. Gastroenterology 133(3):967-75. [PubMed: 17854600] [MGI Ref ID J:128386]
Colony Maintenance
Breeding & Husbandry The strain is maintained by mating homozygous siblings. Some health problems due to liver degeneration begin to arise at about 8 months of age. Expected coat color from breeding:Albino Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
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| Important Note | |
| This strain is homozygous for the retinal degeneration allele Pde6brd1. | |
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| 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. | ||
Purchasing Information
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Contact Information
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Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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