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ABCB11 KO mouse
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Catalogue Number 157774
Antigen/Gene or Protein Targets Abcb11
Disease Keywords Progressive Familial Intrahepatic Cholestasis 2 (PFIC2)
Synonyms spgp/bsep
Model Knock-Out
Relevance Can be used as a genetic model for human Progressive Familial Intrahepatic Cholestasis 2 (a rare and fatal deficiency in the human bile salt transporter). These mice can also be used to study bile formation due to their high sensitivity to bile salt challenge. They can also be used in preclinical screening of choleretic agents.
Production Details The knockout mice were created using gene targeting. Two different ES cell lines were used. TL-1 embryonic stem cells and E14K embryonic stem cells from 129SvyEv mice were generous gifts from Dr. Patricia Labosky (University of Pennsylvania, Philadelphia) and Dr. Tak Mak (Amgen Institute, Toronto), respectively. Genomic DNA of murine spgp gene was isolated from a l phage library of 129/J genomic DNA by using rat spgp cDNA as probe. One of the obtained genomic clones, 129J-9, and an additional fragment of 1.6 kb on the 59 end of 129J-9, which was cloned by PCR amplification, were used to generate the targeting vector (Ref 1, Fig. 1A). Positive selection cassette was pgk-NEO, but no negative cassette was used. The targeting vector was linearized with SstI and electroporated into TL-1 and E14k embryonic stem cells at 340 V and 250 mF of capacitance. ES cell clones surviving G418 selection were screened by Southern blot analysis. Four of the 11 targeted ES cell lines were subsequently used to produce chimeric mice and chimeric mice from three lines with germline transmission were used in this study. The heterozygous mutant mice from each generation were crossed into C57BL/6J. Homozygous mutant mice were produced by intercross of the heterozygous mice. Genotypes of the ES cells and mice were determined by Southern blot analysis using a 1-kb probe upstream of the 59 end.
Breeding Information High mortality in pups and poor breeding performance in triple homozygotes, use heterozygote breeding pairs
Conditional No
Growth/Phenotype Keywords Severe jaundice, blocked bile ducts, high serum bile salts
Strain C57BL/6
Mouse Genetic Background/Cross History C57BL/6J
mice backcrossed to FVB/NJ for more than 22 generations.
Zygosity Homozygous
Research Area Cancer, Cellular Transport, Drug Discovery & Development

References

There are 3 reference entries for this reagent.

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References: 3 entries

 14647060

Lam et al. 2005. Biochemistry. 44(37):12598-605. PMID: 16156672.

Wang et al. 2001. Proc Natl Acad Sci U S A. 98(4):2011-6. PMID: 11172067.


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References: 3 entries

 14647060

Lam et al. 2005. Biochemistry. 44(37):12598-605. PMID: 16156672.

Wang et al. 2001. Proc Natl Acad Sci U S A. 98(4):2011-6. PMID: 11172067.


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