Strain Detail Sheet

Strain Name    :

C.129P2-Pde4dtm1Mct/Mmucd

Stock Number :

034589-UCD

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Pde4dtm1Mct
Name: targeted mutation 1, Marco Conti
Alteration at locus: Knockout
Gene Symbol: Pde4d
Name: phosphodiesterase 4D, cAMP specific
Chromosome: 13
Alteration at locus: Knockout

Genetic Alterations:
A 3.2 kb fragment encompassing exons 8 and 9 was replaced with a PGK-hrpt cassette inserted in the opposite orientation by homologous recombination.

Genotype Determination:

ES Cell Line: E14TG2a

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

Phenotype

Homozygous phenotype: Decreased body weight, postnatal growth retardation, increased cardiac muscle contractility, abnormal ovulation, reduced female fertility, and decreased litter size.

Heterozygous phenotype: None.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Pde4dtm1Mct/Pde4dtm1Mct
        involves: 129P2/OlaHsd
  • cardiovascular system phenotype
    • increased cardiac muscle contractility (MGI Ref ID J:96125)
      • mice have an increased contractile rate in response to isoproterenol compared to wild-type mice
      • treatment with rolipram following isoproterenol does not further alter heart contraction as it does in wild-type mice
      • pertussis toxin enhances heart rate in response to isoproterenol
  • muscle phenotype
    • increased cardiac muscle contractility (MGI Ref ID J:96125)
      • mice have an increased contractile rate in response to isoproterenol compared to wild-type mice
      • treatment with rolipram following isoproterenol does not further alter heart contraction as it does in wild-type mice
      • pertussis toxin enhances heart rate in response to isoproterenol
Pde4dtm1Mct/Pde4dtm1Mct
        involves: 129P2/OlaHsd * 129X1/SvJ
  • mortality/aging
    • partial postnatal lethality (MGI Ref ID J:58116)
      • exacerbated on the 129X1/SvJ background compared to mixed 129P2/OlaHsd and C57BL/6 background; only 9.5% of homozygous null mice are recovered at D30
Pde4dtm1Mct/Pde4dtm1Mct
        involves: 129P2/OlaHsd * C57BL/6
  • mortality/aging
    • partial postnatal lethality (MGI Ref ID J:58116)
      • 13.8% of homozygous null mice are recover ed at D30
  • growth/size phenotype
    • decreased body weight (MGI Ref ID J:58116)
      • 30-40% decrease in body weight at 1-2 wks of age relative to wild-type and heterozygous littermates
    • postnatal growth retardation (MGI Ref ID J:58116)
      • growth rate returns to normal at about 2 wks, though the weight of adult mice remains lower than that of wild-type and heterozygous littermates
  • immune system phenotype
    • immune system phenotype (MGI Ref ID J:106828)
      • response to LPS and thioglycollate is similar to that in wild-type mice
      • abnormal tumor necrosis factor level (MGI Ref ID J:94853)
        • levels of TNF-alpha were significantly reduced at 2 hours after LPS inhalation and remained lower for up to 4 hours compared to controls
      • impaired neutrophil chemotaxis (MGI Ref ID J:94853)
        • chemotaxis in response to KC and macrophage-inflammatory protein-2 was reduced in homozygous mutant neutrophils compared to wild-type
      • impaired neutrophil recruitment (MGI Ref ID J:94853)
        • 48% reduction in the number of neutrophils that are recruited to the lung following LPS inhalation compared to wild-type and homozygous Pde4a mutants
  • reproductive system phenotype
    • abnormal ovulation (MGI Ref ID J:58116)
      • impaired ovulation, yielding few oocytes, after administration of gonadotropins; diminished sensitivity of granulosa cells to gonadotropins
    • decreased litter size (MGI Ref ID J:58116)
    • reduced female fertility (MGI Ref ID J:58116)
  • homeostasis/metabolism phenotype
    • abnormal tumor necrosis factor level (MGI Ref ID J:94853)
      • levels of TNF-alpha were significantly reduced at 2 hours after LPS inhalation and remained lower for up to 4 hours compared to controls

Strain of Origin: 129P2/OlaHsd

Strain genetic background: BALB/c

Suggested Control Mice:

  • Wildtype littermates

Research Applications

  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Endocrine Deficiency
  • Immunology and Inflammation
  • Models for Human Disease
  • Neurobiology
  • Reproduction

Strain Origin

Donor: Marco Conti, MD, University of California at San Francisco

Primary Reference:

  • Bruss MD; Richter W; Horner K; Jin SL; Conti M, Critical role of PDE4D in beta2-adrenoceptor-dependent cAMP signaling in mouse embryonic fibroblasts., J Biol Chem 2008 Aug 15;283(33):22430-42 (Medline PMID: 18508768)
  • Xiang Y; Naro F; Zoudilova M; Jin SL; Conti M; Kobilka B, Phosphodiesterase 4D is required for beta2 adrenoceptor subtype-specific signaling in cardiac myocytes., Proc Natl Acad Sci U S A 2005 Jan 18;102(3):909-14 (Medline PMID: 15644445)
  • Lehnart SE; Wehrens XH; Reiken S; Warrier S; Belevych AE; Harvey RD; Richter W; Jin SL; Conti M; Marks AR, Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias., Cell 2005 Oct 7;123(1):25-35 (Medline PMID: 16213210)

Colony and Husbandry Information

Special Considerations

Random intra-strain mating.

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.

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
034589-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
034589-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
034589-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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