Strain Detail Sheet

Strain Name    :

FVB;129S6-Foxo3tm1.1Rdp/Mmucd

Stock Number :

016132-UCD

Other Names   :

Foxo3a, FVB;129S6-Foxo3tm1.1Rdp/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Foxo3tm1.1Rdp
Name: targeted mutation 1.1, Ronald DePinho
Alteration at locus: Knockout
Gene Symbol: Foxo3
Name: forkhead box O3
Chromosome: 10
Alteration at locus: Knockout

Genetic Alterations:
Deletion of the first coding exon, which encodes the start codon and the Nterminal half of the protein and forkhead DNA binding domain.

Genotype Determination:

ES Cell Line: TC1/TC-1 derived from 129S6/SvEvTac

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

Phenotype

Homozygous phenotype: Female homozygous mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte, early depletion of functional ovarian follicles, and secondary infertility.

Heterozygous phenotype: None


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Foxo3tm1.1Rdp/Foxo3tm1.1Rdp
        involves: 129S6/SvEvTac * FVB/N
  • mortality/aging
    • early reproductive senescence (MGI Ref IDs J:84269, J:118179)
      • females were sterile by 15 weeks of age (MGI Ref ID J:84269)
      • female develop premature sterility due to global activation of primordial follicles soon after birth (MGI Ref ID J:118179)
    • premature death (MGI Ref ID J:118179)
      • mutants with dermatitis survive ~90-95 weeks, while those that remain dermatitis-free survive ~110 weeks compared to heterozygotes or wild-type which can survive past 140 weeks
  • tumorigenesis
    • decreased tumor latency (MGI Ref ID J:118179)
      • 19/20 dermatitis-free mice develop tumors more rapidly (starting at ~25) and show a more rapid onset of tumors compared to mice developing dermatitis (tumors develop at ~90-95 weeks)
    • hemangiosarcoma (MGI Ref ID J:118179)
      • after carcinogen (DMBA) treatment, homozygotes and heterozygotes show increased incidence of angiosarcomas compared to wild-type
    • increased ovary tumor incidence (MGI Ref ID J:118179)
      • females show an increased incidence of ovarian neoplasms (4/16 compared to 0/10 wild-type)
    • increased prolactinoma incidence (MGI Ref ID J:118179)
      • female mice show shorter latency and increased growth of pituitary prolactinomas (7/16 vs 1/10 wild-type)
  • reproductive system phenotype
    • abnormal estrous cycle (MGI Ref ID J:84269)
      • females cycled sporadically from 6 to 15 weeks but became acyclic
      • absent estrous cycle (MGI Ref ID J:84269)
        • females became acyclic after 15 weeks of age
    • abnormal oocyte morphology (MGI Ref ID J:84269)
      • oocytes were observed to be enlarged and misshapen, first evident at 8 days of age
    • abnormal ovarian folliculogenesis (MGI Ref ID J:84269)
      • increased activation resulting in the progression of increased numbers of follicles to more advanced stages of follicular development
      • increased atresia by 8.5 weeks of age
    • early reproductive senescence (MGI Ref IDs J:84269, J:118179)
      • females were sterile by 15 weeks of age (MGI Ref ID J:84269)
      • female develop premature sterility due to global activation of primordial follicles soon after birth (MGI Ref ID J:118179)
    • enlarged ovary (MGI Ref ID J:84269)
      • enlarged ovaries evident by 8 to 14 days of age
    • reduced female fertility (MGI Ref ID J:84269)
      • age dependent decline in female reproductive ability
  • immune system phenotype
    • dermatitis (MGI Ref ID J:118179)
      • mice develop dermatitis between 10-24 months of age; 15/35 mice had to be euthanized due to progressive skin ulcerations
  • hematopoietic system phenotype
    • anemia (MGI Ref ID J:84269)
      • mild compensated anemia
      • he molytic anemia (MGI Ref ID J:118179)
        • mice develop mild hemolytic anemia
    • reticulocytosis (MGI Ref ID J:84269)
  • homeostasis/metabolism phenotype
    • impaired glucose tolerance (MGI Ref ID J:118179)
      • modest glucose intolerance is observed
    • impaired glucose tolerance (MGI Ref ID J:84269)
      • decreased rate of glucose uptake following fast
    • increased circulating follicle stimulating hormone level (MGI Ref ID J:84269)
    • increased circulating luteinizing hormone level (MGI Ref ID J:84269)
  • endocrine/exocrine gland phenotype
    • abnormal ovarian folliculogenesis (MGI Ref ID J:84269)
      • increased activation resulting in the progression of increased numbers of follicles to more advanced stages of follicular development
      • increased atresia by 8.5 weeks of age
    • enlarged ovary (MGI Ref ID J:84269)
      • enlarged ovaries evident by 8 to 14 days of age
  • integument phenotype
    • dermatitis (MGI Ref ID J:118179)
      • mice develop dermatitis between 10-24 months of age; 15/35 mice had to be euthanized due to progressive skin ulcerations

Strain of Origin: 129S6/SvEvTac

Strain genetic background: FVB/N

Strain Development: Foxo3a-/+ animals were backcrossed three times to FVB/n females and progeny of these matings that were Cre- were then intercrossed with littermates to generate the experimental cohort.

Suggested Control Mice: Wild-type littermates

Research Applications

  • Apoptosis
  • Cancer
  • Cardiovascular
  • Cell Biology
  • Dermatology
  • Diabetes/Obesity
  • Endocrine Deficiency
  • Hematology
  • Metabolism
  • Models for Human Disease
  • Reproduction

Strain Origin

Donor: Ron DePinho, M.D., Dana Farber Cancer Institute

Primary Reference:

Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science. 2003 Jul 11;301(5630):215-8. (Medline PMID: 12855809)

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.

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.

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
016132-UCD-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
Litter Recovered litter1; additional fees for any special requests.
016132-UCD-SPERMCryo-preserved spermatozoa
$437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity.2
016132-UCD-EMBRYOCryo-preserved embryos
$1,038.00 / $2,621.00
Non-Profit / For-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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