FVB.129P2-Abcb4^tm1Bor/J

Stock number: 002539
Product name: MDR2 KO
Research areas: Cancer Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

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.

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.

Allele

Symbol: Abcb4^tm1Bor
Name: targeted mutation 1, Piet Borst
MGI accession ID: MGI:1857236
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Abcb4
Marker name: ATP-binding cassette, sub-family B (MDR/TAP), member 4
Chromosome: 5
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.