Strain Detail Sheet

Strain Name    :

B6.129S4-Atp8b1tm1Nbf/Mmucd

Stock Number :

036310-UCD

Other Names   :

C57Bl/6J ATP8B1, B6.129S4-Atp8b1tm1Nbf/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Target: Atp8b1tm1Nbf
Name: targeted mutation 1, Nelson B Freimer
Chromosome: 18
Alteration at locus: Knock-In
Target: Atp8b1
Name: ATPase, class I, type 8B, member 1
Chromosome: 18
Alteration at locus: Knock-In

Genetic Alterations:
We constructed the targeting vector from a 7.1 kb BamHI genomic DNA fragment, derived from a P1 clone [mouse 129/Sv embryonic stem (ES) cell DNA library, Genome Systems, St Louis, MO, USA], encompassing exons 9–12 of Atp8b1. The G923T point mutation was introduced into exon 10 by site-directed mutagenesis. A loxP–neo-loxP resistance cassette (43) was inserted into an intronic BclI restriction site. Linearized vector was electroporated into strain129/SvJae PC-3 ES cells carrying a male-germ-line specific Cre transgene. Recombinant colonies were screened by Southern blot using 5′- and 3′-genomicprobes and a neo probe and by PCR using primers specific for the G923T point mutation. Two independent heterozygous mutant ES cell clones injected into strain C57Bl/6 blastocysts yielded chimeric male mice, which transmitted the targeted allele when bred to C57Bl/6 females. Deletion of the loxP-flanked neoselection cassette from the targeted allele during germline transmission was confirmed by PCR.

Genotype Determination:

ES Cell Line: PC3 derived from 129S4/SvJae

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous: Enlarged livers, elevated serum bile salt, decreased fertility, slower pup growth; upon dietary challenge with bile-salt-supplemented diet, more severe phenotypes, including weight loss, elevated serum bile salts and alkaline phosphatase, and low serum cholesterol.

Heterozygous: No obvious abnormal phenotypes detected.

Strain of Origin: 129S4

Strain genetic background: C57BL/6J

Strain Development: The original mutation was introduced using gene targeting in mouse ES cellsand achieved germ-line transmission of the Atp8b1G923Tneo allele (129S4/SvJae x C57BL/6J)F1 and backcrossed to C57BL/6J. The mutation was maintained by continual backcrossing to C57BL/6J until 22 generations of backcrossing were achieved. Now the current strain is maintained with intercrossing. The phenotypes reported were observed in the N1-N21 generations.

Suggested Control Mice:

  • Wild-type littermates, C57BL/6J 

Research Applications

  • Cell Biology
  • Internal/Organ
  • Metabolism
  • Models for Human Disease
    • progressive familial intrahepatic cholestasis
    • benign recurrent intrahepatic cholestasis
    • extrahepatic abnormalities including hearing loss and pancreatic disease.
  • Sensorineural

Strain Origin

Donor: Laura Bull, Ph.D., University of California, San Francisco

Primary Reference:

Shah S, Sanford UR, Vargas JC, Xu H, Groen A, Paulusma CC, Grenert JP, Pawlikowska L, Sen S, Elferink RP, Bull LN. Strain Background Modifies Phenotypes in the ATP8B1-Deficient Mouse. (2010) PLoS ONE 5(2): e8984. (Medline PMID: 20126555).

Pawlikowska L, Groen AK, Eppens EF, Kunne C, Ottenhoff R, Looije N, Knisely AS, Killeen NP, Bull LN, Elferink RP.  A mouse genetic model for familial cholestasis caused by ATP8B1 mutatons reveals perturbed bile salt homeostasis but no impairment in bile secretion. Hum Mol Genet 15: 881–892.

Groen A, Kunne C, Jongsma G, van den Oever K, Mok KS, Petruzzelli M, Vrins CL, Bull L, Paulusma CC, Oude Elferink RP. Abcg5/8 independent biliary cholesterol excretion in Atp8b1-deficient mice.Gastroenterology. 2008 Jun;134(7):2091-100. Epub 2008 Mar 8.Abcg5/8 independent biliary cholesterol excretion in Atp8b1-deficient mice. (Medline PMID: 18466903).

Colony and Husbandry Information

Special Considerations

None

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Appearance

Coat color: Brown

Other:

Breeding

MMRRC Breeding System: Backcross or Intrastrain mating

Breeding Scheme(s):

  • Heterozygous female x Heterozygous male
  • Heterozygous female x Homozygous male
  • Wild-type C57BL/6J female x Heterozygous male

Generation: N21F1+

Overall Breeding Performance: Good

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: Unknown

Recommended wean age: Unknown

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
036310-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
036310-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
036310-UCD-EMBRYOCryo-preserved embryos
$1,038.00
Non-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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