Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Victor Ling,   British Columbia Cancer Agency

Description
Mice that are homozygous null for the Abcb11 gene suffer from lowered rates of viability and fertility. No Abcb11 gene product (mRNA or protein) is detected in liver tissue. Homozygotes display growth retardation with body weights being 80% that of wildtype littermates at weaning. Lower body weights persist throughout life. Ultrastructural changes are noted in the hepatic canaliculi (lumen dilation, microvilli loss, and accumulation of biliary material). Hepatocytes exhibit increased numbers of peroxisomes, lysosomes and lipid droplets with a concomitant decrease in stored glycogen. Although average bile flow is not significantly reduced, secretion of major hydrophobic bile salts is clearly impaired. An increase in the secretion of tetra-hydroxylated bile acids, cholesterol and phospholipids is observed. These mice provide a model for studying intrahepatic cholestasis and the mechanisims associated with lipid homeostasis.

Development
A targeting vector containing a neomycin resistance cassette in an antisense orientation with respect to the target gene was used to disrupt the region of the Abcb11 gene encoding amino acids 454-478. Three missense mutations and a premature stop codon at amino acid 454 were also introduced. The construct was electroporated into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were backcrossed to C57BL/6LJ animals.

Control Information

	Control
	Wild-type male from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Abcb11^tm1Wng/Abcb11^tm1Wng

        involves: 129S6/SvEvTac * C57BL/6J

• growth/size phenotype
• postnatal growth retardation (MGI Ref ID J:67548)
  • 20% reduction in body weight at time of weaning
• homeostasis/metabolism phenotype
• abnormal circulating cholesterol level (MGI Ref ID J:67548)
  • increased biliary cholesterol concentration
• abnormal phospholipid level (MGI Ref ID J:67548)
  • increased biliary phospholipid concentration
• liver/biliary system phenotype
• abnormal liver morphology (MGI Ref ID J:67548)
  • dilation of canalicalar lumens and partial or complete loss of microvilli
• abnormal hepatocyte morphology (MGI Ref ID J:67548)
  • increased peroxisomes, lysosomes, and lipid droplets
• enlarged liver (MGI Ref ID J:67548)
• abnormal liver physiology (MGI Ref ID J:67548)
  • bile secretion defects

View Research Applications

Research Applications

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

Abcb11^tm1Wng related

Internal/Organ Research
Liver Defects

Research Tools
Internal/Organ Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Abcb11tm1Wng
Allele Name		targeted mutation 1, Renxue Wang
Allele Type		Targeted (knock-out)
Common Name(s)		spgp-;
Mutation Made By		Renxue Wang,   British Columbia Cancer Agency
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Abcb11, ATP-binding cassette, sub-family B (MDR/TAP), member 11
Chromosome		2
Gene Common Name(s)		ABC16; BSEP; Bsep; Lith1; PFIC-2; PFIC2; PGY4; SPGP; bile salt export pump; sister of P-glycoprotein;
Molecular Note		The N-terminal ATP-binding domain, corresponding to amino acids 454-478, was deleted and replaced with a neo cassette. The construct introduced three missense mutations and a premature stop codon at position 454. Western analysis showed no detectable protein in homozygous mice. [MGI Ref ID J:67548]

Genotyping

Genotyping Information

Genotyping Protocols

Abcb11^tm1Wng, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Wang R; Salem M; Yousef IM; Tuchweber B; Lam P; Childs SJ; Helgason CD; Ackerley C; Phillips MJ; Ling V. 2001. Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci U S A 98(4):2011-6. [PubMed: 11172067]  [MGI Ref ID J:67548]

Additional References

Perwaiz S; Forrest D; Mignault D; Tuchweber B; Phillip MJ; Wang R; Ling V; Yousef IM. 2003. Appearance of atypical 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in spgp knockout mice. J Lipid Res 44(3):494-502. [PubMed: 12562825]  [MGI Ref ID J:82194]

Abcb11^tm1Wng related

Lam P; Wang R; Ling V. 2005. Bile acid transport in sister of P-glycoprotein (ABCB11) knockout mice. Biochemistry 44(37):12598-605. [PubMed: 16156672]  [MGI Ref ID J:101161]

Perwaiz S; Forrest D; Mignault D; Tuchweber B; Phillip MJ; Wang R; Ling V; Yousef IM. 2003. Appearance of atypical 3 alpha,6 beta,7 beta,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in spgp knockout mice. J Lipid Res 44(3):494-502. [PubMed: 12562825]  [MGI Ref ID J:82194]

Wang R; Lam P; Liu L; Forrest D; Yousef IM; Mignault D; Phillips MJ; Ling V. 2003. Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein. Hepatology 38(6):1489-99. [PubMed: 14647060]  [MGI Ref ID J:105993]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S6 background and has been backcrossed to C57BL/6J for at least eleven generations (7/01).
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type male from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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