Overview

Also Known As:MDR2 KO

MDR2 KO (Abcb4 or ATP-binding cassette, sub-family B (MDR/TAP), member 4) mice fail to secrete phospholipid into the bile from the liver. Mice develop portal inflammation followed by hepatocellular carcinoma. This strain may be useful in studies of intrahepatic cholestasis and liver cancer.

Donating Investigator

Dr. Piet Borst, The Netherlands Cancer Institute

Genetic overview

Genetic Background	Generation
	N10+pN2F1 (2021-01-07 00:00:00)

Abcb4^tm1Bor

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Abcb4	ATP-binding cassette, sub-family B (MDR/TAP), member 4

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Research Applications

Cancer Research
Metabolism Research
Internal/Organ Research
Research Tools

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 4-week

510.00 Domestic price for breeder pair

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Details

Important Note

This strain is homozygous for the retinal degeneration allele Pde6b^rd1.

Detailed Description

The Abcb4 (ATP-binding cassette, sub-family B (MDR/TAP), member 4) or MDR2 gene encodes a membrane protein that functions as a transporter using phosphatidylcholine as its substrate. MDR2 knock-out (KO) mice lack the ability to secrete phospholipid into the bile from the liver. Homozygotes develop a degenerative liver disease (additional details below). Portal inflammation ensues at an early age followed by hepatocellular carcinoma development after the age of 1 year.
In 1995, the donating investigator reported that homozygotes exhibit liver degeneration beginning around 8 months of age. In 2019, The Jackson Laboratory live colony also observes some incidence of sickly (jaundice) homozygotes as early as 4-5 months of age, and this occurs more frequently in females than males.
Bile from heterozygous mice has half the level of phospholipid when compared to bile from homozygotes. No liver pathology has been shown in heterozygotes.

Development

This strain was developed in the lab of Dr. Piet Borst at The Netherlands Cancer Institute in Amsterdam. The targeting vector was designed to replace exons 1 and 2 of the ATP-binding cassette, sub-family B (MDR/TAP), member 4 locus (Abcb4; MDR2) with a neomycin selection cassette. The translation initiation site is in exon 2. RNase protection assays indicated that mutant truncated transcripts are produced from this allele that contain exons 3-6 or 4-6. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric animals were bred to FVB/N mice. The resulting mice were backcrossed to FVB/N for at least five generations, and then sent to The Jackson Laboratory Repository in 1996. Upon arrival, the colony was additionally backcrossed to FVB/NJ inbred mice (Stock No. 001800). In 2019, the MDR2 KO colony is a total of at least ten generations onto FVB/N.

Control Suggestions

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

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):451-62PubMed: 8106172 MGI: J:15531

View All References

Genetics

Abcb4^tm1Bor

Allele Symbol: Abcb4^tm1Bor

Allele Name	targeted mutation 1, Piet Borst
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	mdr2-; mdr2^neo1; Mdr2ko; Pgy2^tm1Bor
Gene Symbol and Name	Abcb4, ATP-binding cassette, sub-family B (MDR/TAP), member 4
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	5
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.
Mutations Made By	Dr. Piet Borst, The Netherlands Cancer Institute

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

cholecystitis

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

hepatocellular carcinoma

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cancer Research
- Increased Tumor Incidence
  - Hepatomas: hepatacellular carcinoma
  - Hepatomas

Genotype: Abcb4^tm1Bor related

Metabolism Research
Cancer Research
- Toxicology
Internal/Organ Research
- Liver Defects
Research Tools
- Toxicology Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
CAnNCrl.12P2(FVB)-Abcb4

immune system phenotype

enlarged spleen

liver/biliary system phenotype

increased hepatocellular carcinoma incidence
- Background Sensitivity - tumor burden in mice on the BALB/cAnNCrl background is higher than on the FVB/N background
- liver tumors are classified as hepatocellular carcinoma
- Background Sensitivity - mice on the BALB/cAnNCrl background show accelerated development of primary liver cancer compared to mice on the FVB/N background, showing tumors starting at 7 months of age compared to 12 months of age on the FVB/N background

liver fibrosis
- prominent sinusoidal fibrosis starting at 8 weeks of age
- Background Sensitivity - marker analysis indicates that fibrogenic cell activation is amplified in mice on the BALB/cAnNCrl background compared to the FVB/N background
- mice spontaneously develop periductal onion-skin type fibrotic lesions starting from 4 weeks of age
- Background Sensitivity - collagen content in the liver of mice on the BALB/cAnNCrl background is higher at any time point studied compared to mice on the FVB/N background, with total hydroxyproline content about 3-fold higher in the liver than in mice on the FVB/N background
- Background Sensitivity - fibrotic matrix in mice on the BALB/cAnNCrl background is cross-linked to a greater degree than in mice on the FVB/N background
- Background Sensitivity - males exhibit more severe fibrosis than females
- Background Sensitivity - mice on the BALB/cAnNCrl background show accelerated liver fibrosis compared to mice on the FVB/N background, with signs of bridging fibrosis already at 8 weeks and thick septae formation by 12 weeks

portal hypertension
- Background Sensitivity - portal pressure in mice on the BALB/cAnNCrl background increases at a higher pace compared to mice on the FVB/N background, peaking at 12 mmHg at 12 weeks compared to 8.2 mmHg in mice on the FVB/N background
- Background Sensitivity - mice on the BALB/cAnNCrl background show an earlier onset of severe portal hypertension than mice on the FVB/N background

liver cirrhosis
- Background Sensitivity - mice on the BALB/cAnNCrl background show accelerated development of cirrhosis compared to mice on the FVB/N background

cardiovascular system phenotype

portal hypertension
- Background Sensitivity - portal pressure in mice on the BALB/cAnNCrl background increases at a higher pace compared to mice on the FVB/N background, peaking at 12 mmHg at 12 weeks compared to 8.2 mmHg in mice on the FVB/N background
- Background Sensitivity - mice on the BALB/cAnNCrl background show an earlier onset of severe portal hypertension than mice on the FVB/N background

neoplasm

increased hepatocellular carcinoma incidence
- Background Sensitivity - mice on the BALB/cAnNCrl background show accelerated development of primary liver cancer compared to mice on the FVB/N background, showing tumors starting at 7 months of age compared to 12 months of age on the FVB/N background
- liver tumors are classified as hepatocellular carcinoma
- Background Sensitivity - tumor burden in mice on the BALB/cAnNCrl background is higher than on the FVB/N background

growth/size/body region phenotype

weight loss
- mice lose weight at 12 months of age with a 21.5% reduction in weight compared to 2.9% in wild-type mice

enlarged spleen

hematopoietic system phenotype

enlarged spleen

homeostasis/metabolism phenotype

increased circulating bilirubin level
- Background Sensitivity - total bilirubin in serum of aged mice on the BALB/cAnNCrl background is higher at 7 months of age compared to mice on the FVB/N background, and continues to increase through 12 months of age

increased circulating aspartate transaminase level
- increase in serum aspartate aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

increased circulating alkaline phosphatase level
- Background Sensitivity - serum levels of alkaline phosphatase are higher on the BALB/cAnNCrl background and increase with age compared to mice on the FVB/N background which show a decrease in levels by 12 weeks

increased circulating alanine transaminase level
- increase in serum alanine aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)

cardiovascular system phenotype

liver hemorrhage
- beginning at 4 to 6 months

homeostasis/metabolism phenotype

abnormal circulating aspartate transaminase level
- 4-fold increase in aspartate transaminase level

abnormal circulating alanine transaminase level
- 5.8-fold increase in alanine transaminase level

abnormal blood homeostasis
- serum is yellowish, suggesting liver damage

abnormal circulating bilirubin level
- 12-fold elevated bilirubin level; ~50% of this is conjugated

abnormal circulating alkaline phosphatase level
- 3-fold increase in serum alkaline phosphatase level

immune system phenotype

liver inflammation
- portal inflammation with mixed inflammatory infiltrate and slight fibrosis

bile duct inflammation
- inflammation of bile ducts

liver/biliary system phenotype

abnormal bile canaliculus morphology
- bile canaliculi fail to mature remaining wide and smooth unlike in wild-type mice
- prominent widening and increased tortuosity of bile canaliculi with loss of microvilli is present

enlarged liver
- beginning at 4 to 6 months

abnormal hepatocyte morphology
- hepatocyte degeneration, irregular size with nuclear polymorphism and focal necrosis are observed, along with increased proliferation

hepatic necrosis
- beginning at 4 to 6 months

abnormal hepatobiliary system physiology

biliary cirrhosis
- at 3 months, mice exhibit biliary cirrhosis with porto-portal fibrous septa unlike in wild-type mice

abnormal bile composition
- chloride secretion is slightly, but significantly, elevated
- glutathione secretion in bile is ~14% of wild-type
- phospolipid to bile salt ratio is only ~41% of wild-type
- absence of phospholipid secretion in bile, lipid secretion is decreased and there is a 15-reduction in cholesterol secretion in bile

abnormal hepatobiliary system morphology

abnormal portal triad morphology
- at 3 months, mice exhibit expansion of the portal triad unlike in wild-type mice

bile duct inflammation
- inflammation of bile ducts

bile duct proliferation
- mice exhibit ductular proliferation and portal inflammation with mixed inflammatory infiltrate unlike in wild-type mice

dilated bile duct
- larger bile ducts are dilated

increased hepatocellular carcinoma incidence
- beginning at 4 to 6 months, mice develop hepatocellular carcinoma with necrosis, hemorrhage, and strong cytonuclear polymorphism unlike in wild-type mice
- mice exhibit lung metastasis

liver inflammation
- portal inflammation with mixed inflammatory infiltrate and slight fibrosis

cholestasis

intrahepatic cholestasis
- moderate liver damage with cholestatic properties (raised serum-conjugated bilirubin) is observed

liver hemorrhage
- beginning at 4 to 6 months

abnormal bile duct morphology
- portal expansion due to ductular proliferation is seen

abnormal bile secretion

cellular phenotype

hepatic necrosis
- beginning at 4 to 6 months

endocrine/exocrine gland phenotype

abnormal bile duct morphology
- portal expansion due to ductular proliferation is seen

bile duct proliferation
- mice exhibit ductular proliferation and portal inflammation with mixed inflammatory infiltrate unlike in wild-type mice

dilated bile duct
- larger bile ducts are dilated

neoplasm

increased hepatocellular carcinoma incidence
- mice exhibit lung metastasis
- beginning at 4 to 6 months, mice develop hepatocellular carcinoma with necrosis, hemorrhage, and strong cytonuclear polymorphism unlike in wild-type mice

reproductive system phenotype

reduced female fertility
- at 4 months

growth/size/body region phenotype

enlarged liver
- beginning at 4 to 6 months

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
involves: 129P2/OlaHsd * BALB/c

cardiovascular system phenotype

decreased systemic arterial systolic blood pressure
- mice treated with propranolol long-term show a minor reduction in the average systolic blood pressure without impact on viability

immune system phenotype

bile duct inflammation
- propranolol treatment reduces inflammation
- mice develop sclerosing cholangitis

liver/biliary system phenotype

bile duct inflammation
- propranolol treatment reduces inflammation
- mice develop sclerosing cholangitis

liver fibrosis
- mice develop periportal fibrosis after 3 months of age, characterized by onion skin-like matrix formation around the bile ducts
- propranolol treatment improves liver architecture and reduces inflammation and fibrosis progression
- after 5 months, septal formation and massive matrix deposition is seen around ducts in the liver and at 8 months, periportal fibrosis is frequently accompanied by septae formation and prominent proliferation of the bile ducts

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
involves: 129P2/OlaHsd * FVB/N

cellular phenotype

focal hepatic necrosis
- focal necrosis with formation of eosinophilic bodies

immune system phenotype

bile duct inflammation
- cholangitis

liver inflammation
- portal inflammation

liver/biliary system phenotype

bile duct inflammation
- cholangitis

focal hepatic necrosis
- focal necrosis with formation of eosinophilic bodies

intrahepatic cholestasis

liver inflammation
- portal inflammation

abnormal hepatocyte morphology
- hepatocytes show irregular nuclear polymorphism

digestive/alimentary phenotype

abnormal intestine physiology
- sodium concentrations in the ileal lumen are increased
- mice exhibit an increase in taurocholic acid uptake in the ileum, indicating an increase in bile acid uptake

abnormal feces composition
- daily bile acid disposal in feces is decreased

decreased intestinal cholesterol absorption
- 40% reduction in absorption efficiency

homeostasis/metabolism phenotype

abnormal sodium ion homeostasis
- sodium concentrations in the ileal lumen are increased

decreased circulating cholesterol level
- plasma levels reduced

decreased intestinal cholesterol absorption
- 40% reduction in absorption efficiency

increased circulating alanine transaminase level

abnormal lipid homeostasis

increased circulating aspartate transaminase level

abnormal circulating enzyme level

increased bile salt level
- increase in concentration of bile acids in the plasma and the liver
- pool size of bile acids is increased

increased circulating bilirubin level

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
C.129P2-Abcb4

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme activity
- elevation in serum activities of liver enzymes, including aminotransferase and alkaline phosphatase

decreased circulating calcium level

increased alkaline phosphatase activity

decreased vitamin D level
- 25(OH)-vitamin D serum concentrations are almost 50% lower than in wild-type mice

increased circulating phosphate level

increased transforming growth factor beta level
- increase in serum levels of activated TGF-beta until the age of 30 weeks which subsequently declines to basal levels by 45 weeks of age compared to wild-type mice which show a continuous decrease throughout life

liver/biliary system phenotype

liver fibrosis
- liver damage increases most rapidly in the first 15 weeks of life and then progresses slowly thereafter

skeleton phenotype

abnormal compact bone morphology
- females exhibit a decrease in cortical bone density and a lower circumference of the bone at the exact mid-diaphysis (periosteal circumference), resulting in normal thickness of the cortical bone

abnormal trabecular bone morphology
- with increasing age, changes in trabecular order and connectivity are seen with reduced mineralization of the trabecular bone meshwork
- increase in trabecular separation at 20 weeks of age
- trabecular tissue mineral density is lower at 30 weeks of age

decreased bone mineral content
- decrease in femoral mineral contents
- reduction of whole body bone mineral content in males and of bone fractions of the total tissue weights in females at 15 weeks of age

decreased bone volume
- decrease in femoral mineral contents and in total femoral volume at 15 weeks of age, thus total femoral volume bone mineral density is not affected

decreased bone mineral density
- females fed a vitamin D insufficient diet exhibit decreased femoral bone and cortical bone mineral density, compared to wild-type mice on the same diet
- vitamin D supplementation does not restore bone abnormalities

decreased trabecular bone connectivity density
- connective density is lower at 20 weeks of age

abnormal bone remodeling
- mutants exhibit altered gene expression of bone modeling markers and an increase in serum levels of the osteoclastogenesis inducing factor RANKL, indicating impaired bone remodeling

decreased bone trabecula number
- decrease in trabecular numbers at 20 weeks of age

abnormal trabecular bone volume
- changes in trabecular bone volume fractions are seen at 5 weeks of age but not in older mice, however trabecular thickness does not differ from wild-type

The following phenotype relates to a compound genotype created using this strain

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
FVB.129P2-Abcb4/J

growth/size/body region phenotype

enlarged liver

enlarged spleen

hematopoietic system phenotype

enlarged spleen

homeostasis/metabolism phenotype

increased circulating alkaline phosphatase level
- Background Sensitivity - serum levels of alkaline phosphatase are lower on the FVB/N background and show a decrease in levels by 12 weeks compared to mice on the BALB/cAnNCrl background in which levels increase with age

increased circulating aspartate transaminase level
- increase in serum aspartate aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

abnormal circulating enzyme level
- elevated serum transaminase levels

increased circulating alanine transaminase level
- increase in serum alanine aminotransferase is similar on both the BALB/cAnNCrl and FVB/N backgrounds

increased circulating bilirubin level
- slight increase
- Background Sensitivity - total bilirubin in serum of aged mice on the FVB/N background is lower at 7 months of age compared to mice on the BALB/cAnNCrl background

cardiovascular system phenotype

portal hypertension
- Background Sensitivity - portal pressure in mice on the FVB/N background increases at a slower pace compared to mice on the BALB/cAnNCrl background
- Background Sensitivity - mice on the FVB/N background show a later onset of severe portal hypertension than mice on the BALB/cAnNCrl background

immune system phenotype

bile duct inflammation
- progressive sclerosing cholangitis

enlarged spleen

digestive/alimentary phenotype

abnormal feces composition
- fecal acidic sterol levels are decreased 30% compared to in wild-type mice
- Normal - however, fecal neutral sterol levels are normal

liver/biliary system phenotype

abnormal gallbladder size
- gallbladders are 3 times larger than in wild-type mice at 9 weeks of age
- over time, gallbladder size decreases in males, but not females, such that at 18 weeks of age, some males at 18 weeks of age have very small gallbladders filled with sticky mucin gel and needle-like crystals

gallstones
- 50% and 80% of females at 12 and 15 weeks of age, respectively, exhibit gallstones in the gallbladder biles and by 18 weeks, all females have gallstones
- core of stones are composed of needle-like crystals and gelled mucin
- stone number and size are higher in females than males
- 42% of 7-10 month old females, but not males, develop choledocholithiasis
- males form gallstones later, after 15 weeks of age, and with lower prevalence rates than in females
- number of gallstones per mouse ranges from 1-8 with an average of 1.3 +/- 0.3 stones per mouse and most gallstones are smaller than 0.1 mm

liver fibrosis
- Background Sensitivity - fibrotic matrix in mice on the FVB/N background is cross-linked to a lesser degree than in mice on the BALB/cAnNCrl background
- mice spontaneously develop periductal onion-skin type fibrotic lesions starting from 4 weeks of age
- Background Sensitivity - collagen content in the liver of mice on the FVB/N background is lower at any time point studied compared to mice on the BALB/cAnNCrl background
- Background Sensitivity - females exhibit more severe fibrosis than males
- Background Sensitivity - mice on the FVB/N background show slower progression of liver fibrosis compared to mice on the BALB/cAnNCrl background
- prominent sinusoidal fibrosis starting at 8 weeks of age
- Background Sensitivity - marker analysis indicates that fibrogenic cell activation is lower in mice on the FVB/N BALB/cAnNCrl background compared to the BALB/cAnNCrl background

portal hypertension
- Background Sensitivity - mice on the FVB/N background show a later onset of severe portal hypertension than mice on the BALB/cAnNCrl background
- Background Sensitivity - portal pressure in mice on the FVB/N background increases at a slower pace compared to mice on the BALB/cAnNCrl background

abnormal bile composition
- gallbladder bile precipitates solid crystals, with males forming these needle-like crystals later (after 15 weeks) than females (after 12 weeks of age) and with a lower prevalence than in females
- phosphatidylcholine (PC) concentrations in the gallbladder biles are decreased, and the relative compositions shift to greater proportions of the more hydrophobic PC-(18:0-18:2) and PC-(18:0-20:4)
- 33% and 60% of females at 12 and 15 weeks of age, respectively, exhibit needle-like crystals in the gallbladder biles
- bile cholesterol levels are decreased compared to in wild-type mice
- females exhibit a more hydrophobic bile salt pool due to lower tauro-beta-muricholate levels in bile

increased hepatocellular carcinoma incidence
- Background Sensitivity - mice on the FVB/N background show slower development of primary liver cancer compared to mice on the BALB/cAnNCrl background, showing tumors starting at 12 months of age compared to 7 months of age on the BALB/cAnNCrl background
- liver tumors are classified as hepatocellular carcinoma
- Background Sensitivity - tumor burden in mice on the FVB/N background is lower than on the BALB/cAnNCrl background

abnormal liver morphology
- cholestatic liver damage
- mature mice develop intrahepatic stones, which are composed of needle-like crystals like the gallbladder stones

enlarged liver

liver cirrhosis
- Background Sensitivity - mice on the FVB/N background show slower development of cirrhosis compared to mice on the BALB/cAnNCrl background

abnormal bile duct morphology
- 42% of 7-10 month old females, but not males, develop choledocholithiasis (bile duct stones)
- mice exhibit proliferation of bile ducts, accompanied by periportal and periductal fibrosis, resulting in fibro-obliteration and segmental strictures of bile duct

intrahepatic cholestasis
- occluded intrahepatic bile ducts filled with crystalline occlusions composed of needle-like crystals and mucin gel

bile duct inflammation
- progressive sclerosing cholangitis

dilated bile duct
- dilated extrahepatic duct in 7 month old females

endocrine/exocrine gland phenotype

abnormal bile duct morphology
- 42% of 7-10 month old females, but not males, develop choledocholithiasis (bile duct stones)
- mice exhibit proliferation of bile ducts, accompanied by periportal and periductal fibrosis, resulting in fibro-obliteration and segmental strictures of bile duct

abnormal gallbladder size
- gallbladders are 3 times larger than in wild-type mice at 9 weeks of age
- over time, gallbladder size decreases in males, but not females, such that at 18 weeks of age, some males at 18 weeks of age have very small gallbladders filled with sticky mucin gel and needle-like crystals

dilated bile duct
- dilated extrahepatic duct in 7 month old females

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - mice exhibit normal plasma levels of sitosterol and campesterol

neoplasm

increased hepatocellular carcinoma incidence
- Background Sensitivity - mice on the FVB/N background show slower development of primary liver cancer compared to mice on the BALB/cAnNCrl background, showing tumors starting at 12 months of age compared to 7 months of age on the BALB/cAnNCrl background
- Background Sensitivity - tumor burden in mice on the FVB/N background is lower than on the BALB/cAnNCrl background
- liver tumors are classified as hepatocellular carcinoma

References

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):451-62PubMed: 8106172 MGI: J:15531

Additional References

Borst P; Schinkel AH. 1996. What have we learnt thus far from mice with disrupted P-glycoprotein genes? Eur J Cancer 32A(6):985-90PubMed: 8763339 MGI: 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):261-74PubMed: 15236191 MGI: J:93576

Additional - Abcb4^tm1Bor related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Abcb4 alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining our live colony, heterozygous mice are bred to wildtype mice from the colony or to FVB/NJ inbred mice (Stock No. 001800). [October 2020]

In 1995, the donating investigator reported that homozygotes exhibit liver degeneration beginning around 8 months of age.
In 2019, The Jackson Laboratory live colony also observes some incidence of sickly (jaundice) homozygotes as early as 4-5 months of age, and this occurs more frequently in females than males.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Wild-type
- Wild-type x Heterozygote
Appearance
- albino
  Related Genotype: Tyr^c/Tyr^c
Citation
When using the MDR2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002539 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX18 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous and Wildtype for Abcb4<tm1Bor>

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:MDR2 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Abcb4tm1Bor

Allele Symbol: Abcb4tm1Bor

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Abcb4tm1Bor related

Mammalian Phenotype Terms by Genotype

Genotype: Abcb4tm1Bor/Abcb4tm1BorCAnNCrl.12P2(FVB)-Abcb4

immune system phenotype

liver/biliary system phenotype

cardiovascular system phenotype

neoplasm

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Abcb4tm1Bor/Abcb4tm1Boreither: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

cellular phenotype

endocrine/exocrine gland phenotype

neoplasm

reproductive system phenotype

growth/size/body region phenotype

Genotype: Abcb4tm1Bor/Abcb4tm1Borinvolves: 129P2/OlaHsd * BALB/c

cardiovascular system phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Abcb4tm1Bor/Abcb4tm1Borinvolves: 129P2/OlaHsd * FVB/N

cellular phenotype

immune system phenotype

liver/biliary system phenotype

digestive/alimentary phenotype

homeostasis/metabolism phenotype

Genotype: Abcb4tm1Bor/Abcb4tm1BorC.129P2-Abcb4

homeostasis/metabolism phenotype

liver/biliary system phenotype

skeleton phenotype

Genotype: Abcb4tm1Bor/Abcb4tm1BorFVB.129P2-Abcb4/J

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cardiovascular system phenotype

immune system phenotype

digestive/alimentary phenotype

liver/biliary system phenotype

endocrine/exocrine gland phenotype

mammalian phenotype

neoplasm

References

Additional References

Additional - Abcb4tm1Bor related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Abcb4^tm1Bor

Allele Symbol: Abcb4^tm1Bor

Genotype: Abcb4^tm1Bor related

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
CAnNCrl.12P2(FVB)-Abcb4

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
involves: 129P2/OlaHsd * BALB/c

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
involves: 129P2/OlaHsd * FVB/N

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
C.129P2-Abcb4

Genotype: Abcb4^tm1Bor/Abcb4^tm1Bor
FVB.129P2-Abcb4/J

Additional - Abcb4^tm1Bor related