Strain Detail Sheet

Strain Name:
B6J.129S6(Cg)-C1qbptm1.2Ypz/Mmnc
Stock Number:
067997-UNC
Citation ID:
RRID:MMRRC_067997-UNC
Other Names:
p32 (C1QBP) knockout

Strain Information

Gene Details

C1qbptm1.2Ypz
Name: complement component 1, q subcomponent binding protein; targeted mutation 1.2, Yangping Zhang
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Knockout
C1qbp
Name: complement component 1, q subcomponent binding protein
Synonyms: D11Wsu182e, P32, HABP1
Type: Gene
Species: Mouse
Chromosome: 11
Alteration at locus: Knockout
NCBI: 12261
HGNC: HGNC:1243
Homologene: 31023
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Genetic Alterations

Conditional-ready allele using targeted substitution in the C1qbp gene (aka p32 gene): an FRT-flanked neomycin resistance cassette with a 3' loxP site was inserted upstream of exon 3. An additional loxP site was inserted downstream of exon 3. Flp-mediated recombination removed the selection cassette; Cre-mediated recombination deleted exon 3.

Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
    • ES Cell Line
    Not specified

    Strain Description

    Phenotype
    Animals with the floxed allele show a wild-type phenotype.

    The whole-body deletion of the p32 results in an embryonic lethal phenotype. Heterozygous mice (p32 +/−) are resistant to age- and high-fat diet-induced ailments, including obesity, hyperglycemia, and hepatosteatosis. Notably, p32 +/− mice are apparently healthy, demonstrate an increased lean-to-fat ratio, and show dramatically improved insulin sensitivity despite prolonged high-fat diet feeding. Also observed were increased oxygen consumption and heat production, indicating that heterozygotes expend more energy. The analysis revealed that haploinsufficiency for p32 impairs glucose oxidation, which results in a compensatory increase in fatty acid oxidation and glycolysis. These metabolic alterations increase both aerobic and anaerobic energy expenditure. Collectively, the data show that p32 plays a critical role in energy homeostasis and represents a potential novel target for the development of anti-obesity drugs.
    MeSH Terms
    • Animals
    • Diet, High-Fat/adverse effects
    • Energy Intake/genetics
    • Energy Metabolism/genetics
    • Glycolysis/genetics
    • Heterozygote
    • Homeostasis/genetics
    • Hyperglycemia/etiology
    • Hyperglycemia/genetics
    • Hyperglycemia/metabolism
    • Insulin Resistance/genetics
    • Mice, Inbred C57BL
    • Mice, Knockout
    • Mitochondrial Proteins/genetics
    • Mitochondrial Proteins/metabolism
    • Obesity/etiology
    • Obesity/genetics
    • Obesity/metabolism
    • Oxygen Consumption/genetics
    • 3T3 Cells
    • Acetyl-CoA Carboxylase/genetics
    • Acetyl-CoA Carboxylase/metabolism
    • Cell Line, Tumor
    • Cells, Cultured
    • Down-Regulation
    • Endoplasmic Reticulum Stress
    • Fatty Acid Synthase, Type I/genetics
    • Fatty Acid Synthase, Type I/metabolism
    • Homeostasis
    • Humans
    • Lipid Metabolism
    • Mice
    • Sterol Regulatory Element Binding Protein 1/genetics
    • Sterol Regulatory Element Binding Protein 1/metabolism
    • alpha-Glucosidases/genetics
    • alpha-Glucosidases/metabolism
    • Apoptosis
    • Carrier Proteins/genetics
    • Carrier Proteins/metabolism
    • Exons
    • Hyaluronan Receptors/genetics
    • Hyaluronan Receptors/metabolism
    • Membrane Potential, Mitochondrial
    • Mitochondria/metabolism
    • Mitochondria/pathology
    • Mutation
    • Protein Binding
    • Protein Structure, Tertiary
    • Protein Transport
    • RNA Interference
    • RNA, Small Interfering/metabolism
    • Signal Transduction
    • Transfection
    • Tumor Suppressor Protein p14ARF/genetics
    • Tumor Suppressor Protein p14ARF/metabolism
    • Tumor Suppressor Protein p53/genetics
    • Tumor Suppressor Protein p53/metabolism
    Strain Development

    The development is based on unspecified ESCs derived from 129S6/SvEvTac. Male chimeric mice were mated to C57BL/6J females and resulted in heterozygous agouti mice. The heterozygous F1 agouti females were mated to B6N.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/J (RRID:IMSR_JAX:016226) male to delete the neo cassette. Crossing to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J (RRID:IMSR_JAX:003724) was used to knock out the gene. p32 heterozygous (neo-) males were used to initiate five backcrosses to C57BL/6J mice with selected deletion of the p32 allele. Maintenance on C57BL/6J background to N12 thereafter.

    Suggested Control Mice
    C57BL/6J

    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@med.unc.edu. Older strains may not have this information.

    Research Applications

    • Diabetes
    • Metabolism
    • Obesity

    Strain Origin

    Donor
    Yanping Zhang, Ph.D., University of North Carolina at Chapel Hill.
    Primary Reference

    Liu Y, Leslie PL, Jin A, Itahana K, Graves LM, Zhang Y. p32 heterozygosity protects against age- and diet-induced obesity by increasing energy expenditure. Sci Rep. 2017 Jul 18;7(1):5754. doi: 10.1038/s41598-017-06209-9. (Medline PMID: 28720899)

    Liu Y, Leslie PL, Jin A, Itahana K, Graves LM, Zhang Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression. FASEB J. 2018 Jul;32(7):3892-3902. doi: 10.1096/fj.201701004RR. Epub 2018 Feb 20. (Medline PMID: 29465311)

    Itahana K, Zhang Y. Mitochondrial p32 is a critical mediator of ARF-induced apoptosis. Cancer Cell. 2008 Jun;13(6):542-53. doi: 10.1016/j.ccr.2008.04.002. (Medline PMID: 18538737)

    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_health@med.unc.edu.

    Appearance

    Coat Color
    Black
    Eye
    Black

    Breeding

    MMRRC Breeding System
    Backcross
    Generation
    N12 (C57BL/6J), F2
    Overall Breeding Performance
    Good

    Reproductive Statistics

    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: No No
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 7 to 9 months 10 to 12 months
    Average litter size
    7 to 9
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    7 to 9

    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@med.unc.edu for more information.

    A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Jacqueline Quay.

    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.

    A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Jacqueline Quay

    Fees

    - Products for this strain are Not Yet Available for Ordering
    - If you register interest in this strain, you will be notified when it becomes available for ordering.
    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.