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.
Dr. Piet Borst, The Netherlands Cancer Institute
This strain is homozygous for the retinal degeneration allele Pde6brd1.
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.
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.
|Allele Name||targeted mutation 1, Piet Borst|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||mdr2-; mdr2neo1; Mdr2ko; Pgy2tm1Bor|
|Gene Symbol and Name||Abcb4, ATP-binding cassette, sub-family B (MDR/TAP), member 4|
|Strain of Origin||129P2/OlaHsd|
|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
The strain is maintained by mating homozygous siblings. 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.
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.
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