Strain Detail Sheet

Strain Name:
B6J.129S7-Pcsk1ntm1Jep/Mmnc
Stock Number:
044012-UNC
Citation ID:
RRID:MMRRC_044012-UNC
Other Names:
Pcsk1n

Strain Information

Gene Details

Pcsk1ntm1Jep
Name: proprotein convertase subtilisin/kexin type 1 inhibitor; targeted mutation 1, John E Pintar
Type: Allele
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: Knockout
Pcsk1n
Name: proprotein convertase subtilisin/kexin type 1 inhibitor
Synonyms: basic protein IA-4, proSAAS, Pan3
Type: Gene
Species: Mus musculus (mouse)
Chromosome: X
Alteration at locus: Knockout
NCBI: 30052
Homologene: 8315
Genome Browser [Click image to go to Jbrowse]



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Genetic Alterations
Targeted disruption of Pcsk1n on the X chromosome.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
    • ES Cell Line
    AB2.2

    Strain Description

    Phenotype
    1. Male proSAAS (Pcsk1n) knockout (KO) mice have decreased body weight, but maintain normal fasting blood glucose levels and are able to efficiently clear glucose from the blood in response to a glucose challenge (PMID:20367757).
    2. Responses to psychostimulants were examined. Acute administration of cocaine or amphetamine-stimulated locomotor activity more robustly in wild-type (WT) compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was present in both genotypes; however, proSAAS KO mice failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were abnormal, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. (PMID:28881029)
    3. ProSAAS KO display anxiety-like behavior in the zero maze and diazepam dos not fully normalize the behavior. Spontaneous locomotor and rearing activities in the open field are reduced in mutants. The proSAAS KO mice are deficient in cued, but not contextual, fear conditioning and are impaired in fear-potentiated startle. The mutants displayed abnormal circadian rhythms and did not entrain to a light pulse when placed in complete darkness for 55 days (unpublished).
    Mammalian Phenotype Terms
    Allelic Composition: (Genetic Background: )
    MeSH Terms
    • Adrenocorticotropic Hormone/metabolism
    • Alleles
    • Animals
    • Antigens, Differentiation, B-Lymphocyte/metabolism
    • Blood Glucose/metabolism
    • Blotting, Western
    • Body Weight/physiology
    • Brain Chemistry/drug effects
    • Brain Chemistry/physiology
    • Embryonic Stem Cells/physiology
    • Female
    • Fetus/metabolism
    • Gene Targeting
    • Histocompatibility Antigens Class II/metabolism
    • Male
    • Mice
    • Mice, Knockout
    • Motor Activity/physiology
    • Nerve Tissue Proteins/physiology
    • Neuropeptides/metabolism
    • Peptides/chemistry
    • Peptides/isolation & purification
    • Proprotein Convertase 1/metabolism
    • Protein Processing, Post-Translational/physiology
    • Radioimmunoassay
    • Transfection
    Strain Development
    A targeting vector for disrupting proSAAS (Pcsk1n) was constructed by subcloning two genomic fragments of proSAAS into a pKO Scrambler V919 targeting vector. A 2.5-kb XbaI/SacII fragment located 5' of exon 1 was inserted into XbaI/SacII sites in the targeting vector. A neomycin resistance cassette and Herpes Simplex Virus thymidine kinase (HSV-TK) cassette were subcloned into AscI (neomycin) and RsrII (Herpes Simplex Virus thymidine kinase) sites in the knock-out (KO) vector. A 5.5-kb XbaI genomic fragment downstream of exon 1 was subcloned into pBluescript, excised with NotI and KpnI, and then subcloned into BglII (blunt) and KpnI sites within the KO vector. The targeting vector was linearized and electroporated into AB2.2 embryonic stem cells (Lexicon Genetics, Woodlands, TX, USA). Embryonic stem (ES) cells and mouse genotypes were determined by Southern blotting using a probe located outside (5') of the genomic sequence used to construct the targeting vector (PMID:20367757). The mice have been backcrossed onto a C57BL/6J background for >7 generations.
    Suggested Control Mice
    Since Pcsk1n is on the X chromosome, the donor bred heterozygous females with wild-type Pcsk1n males to obtain heterozygous and wild-type pups. Heterozygous females were bred with homozygous mutant Pcsk1n males to obtain heterozygous and homozygous mutant pups.

    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

    • Neurobiology

    Strain Origin

    Donor
    Lloyd Fricker, Ph.D Albert Einstein College of Medicine
    Primary Reference

    Morgan DJ, Wei S, Gomes I, Czyzyk T, Mzhavia N, Pan H, Devi LA, Fricker LD,Pintar JE. The propeptide precursor proSAAS is involved in fetal neuropeptideprocessing and body weight regulation. J Neurochem. 2010 Jun;113(5):1275-84. doi:10.1111/j.1471-4159.2010.06706.x. Epub 2010 Mar 26. PubMed PMID: 20367757; PubMedCentral (Medline PMCID: PMC3510705)

    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
    Random intra-strain mating
    Generation
    N7+F5
    Overall Breeding Performance
    Excellent

    Reproductive Statistics

    NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Undetermined Yes
    Hetero/Hemizygotes are fertile: Yes Yes
    Age Reproductive Decline: 8 to 12 months 8 to 12 months
    Average litter size
    7-9
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    5-9

    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.

    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.

    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
    044012-UNC-SPERM Cryo-preserved spermatozoa $564.00 / $937.00
    Non-Profit / For-Profit    		 Aliquot Approximate quantity3
    044012-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / $4,837.00
    Non-Profit / For-Profit    		 Litter Recovered litter4; additional fees for any special requests.
    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.

    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.