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Strain Detail Sheet

Strain Name:
129S/Sv-Atp8b1tm1Nbf/Mmucd
Stock Number:
036309-UCD
Citation ID:
RRID:MMRRC_036309-UCD
Other Names:
ATP8B1, 129S1-Atp8b1tm1Nbf/Mmcd

Strain Information

Gene Details

Atp8b1tm1Nbf
Name: ATPase, class I, type 8B, member 1; targeted mutation 1, Nelson B Freimer
Synonyms: Atp8b1G308V
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 18
Alteration at locus: Knock-In
Atp8b1
Name: ATPase, class I, type 8B, member 1
Synonyms: FIC1, Ic
Type: Gene
Species: Mouse
Chromosome: 18
Alteration at locus: Knock-In
NCBI: 54670
VEGA: 18
HGNC: HGNC:3706
Homologene: 21151

Additional Resources
IMPC
Google
Entrez
PubMed
IMSR
Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
Genetic Alterations
A G to T transversion at bp 923 in Atp8b1 exon 10 resulting in the substitution of a valine for a glycine at amino acid 308 (G308V) was introduced via homologous recombination. Targeting took place in ES cells homozygous for the Tg(Prm-cre)70Og transgene, which expresses Cre recombinase in male germ cells. A floxed neo cassette inserted into intron 11 during homologous recombination in ES cells was subsequently excised by Cre-mediated recombination upon transmission from male chimeric mice. RT-PCR confirmed that RNA expression is normal however western blot analysis demonstrated that protein expression was absent in the liver and almost absent in the ileum.
Genotype Determination

Genotyping Protocol

ES Cell Line
PC3 (129S4/SvJae-Tg(Prm-cre)70Og)

Strain Description

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.
Mammalian Phenotype Terms
Allelic Composition: Atp8b1tm1Nbf/Atp8b1tm1Nbf (Genetic Background: involves: 129S1/SvImJ * 129S4/SvJae )
Allelic Composition: Atp8b1tm1Nbf/Atp8b1tm1Nbf (Genetic Background: involves: 129S4/SvJae )
MeSH Terms
  • Adenosine Triphosphatases/deficiency
  • Adenosine Triphosphatases/genetics
  • Alkaline Phosphatase/blood
  • Animals
  • Animals, Newborn
  • Bilirubin/blood
  • Cholates/administration & dosage
  • Cholestasis, Intrahepatic/enzymology
  • Cholestasis, Intrahepatic/genetics
  • Cholestasis, Intrahepatic/pathology
  • Cholesterol/blood
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Liver/drug effects
  • Liver/pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Phenotype
  • Phospholipid Transfer Proteins
  • Species Specificity
  • Survival Analysis
  • Weight Gain/drug effects
  • ATP Binding Cassette Transporter, Sub-Family G, Member 5
  • ATP Binding Cassette Transporter, Sub-Family G, Member 8
  • ATP-Binding Cassette Transporters/genetics
  • ATP-Binding Cassette Transporters/metabolism
  • Adenosine Triphosphatases/metabolism
  • Bile/enzymology
  • Bile/metabolism
  • Bile Acids and Salts/blood
  • Bile Canaliculi/metabolism
  • Cell Membrane/metabolism
  • Cholesterol/metabolism
  • DNA-Binding Proteins/agonists
  • DNA-Binding Proteins/metabolism
  • Hydrocarbons, Fluorinated
  • Lipoproteins/deficiency
  • Lipoproteins/genetics
  • Lipoproteins/metabolism
  • Liver/enzymology
  • Liver/metabolism
  • Liver X Receptors
  • Membrane Fluidity
  • Orphan Nuclear Receptors
  • Phospholipids/metabolism
  • Receptors, Cytoplasmic and Nuclear/agonists
  • Receptors, Cytoplasmic and Nuclear/metabolism
  • Sulfonamides/pharmacology
  • Time Factors
  • Up-Regulation
Strain Development
The donating investigators 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), 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 was inserted into an intronic BclI restriction site. Linearized vector was electroporated into strain 129/SvJae PC-3 ES cells carrying a male-germ-line specific Cre transgene. Recombinant colonies were screened by Southern blot using 5′- and 3′-genomic probes 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.

The original mutation was introduced using gene targeting in mouse ES cells and achieved germ-line transmission of the Atp8b1G923Tneo allele (129S4/SvJae x 129S1/SvImJ)F1 and backcrossed to 129S1/SvImJ. The mutation was maintained by continual backcrossing to 129S1/SvImJ until 21 generations of backcrossing were achieved.
Suggested Control Mice
Wild-type littermates

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.

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. PLoS One. 2010 Feb 1;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. (Medline PMID: 18466903).

Colony and Husbandry Information

Health Status Report

Colony Surveillance Program and Current Health Reports

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

Breeding

MMRRC Breeding System
Backcross, Donor now maintains the colony with Intra-strain Random Mating
Breeding Scheme(s)

Wild-type (29S1/SvImJ) female x Heterozygous male or reciprocal mating

Wild-type female x Heterozygous male from the colony or reciprocal mating

Homozygous female x Homozygous male from the colony

Generation
N21F1+
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
Undetermined
Recommended wean age
3 weeks

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.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Conditions of Distribution

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 $)
*Shipping & Handling not included*		 Units Notes
036309-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
036309-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
036309-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; 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 contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 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.

4 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.

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.