ABCB11 KO mouse

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

Contributors

Inventor Institute
Victor Ling BC Cancer
SKU: 157774
Product description: 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.
Alternate name: spgp/bsep
Conditional: No
Genetic background: 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.
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.
Cat. #: 157774
Research Fields: Cancer; Cell biology; Drug development
Target: Abcb11
Disease: Progressive Familial Intrahepatic Cholestasis 2 (PFIC2)
Model: Knock-Out
Zygosity: Homozygous
Strain: C57BL/6
Phenotype: Severe jaundice, blocked bile ducts, high serum bile salts
Shipping conditions: Embryo/Spermatoza- Dry Ice
References:

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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