Strain Detail Sheet

Strain Name    :

B6.129X1-Prkar1atm1Gsm/Mmucd

Stock Number :

000413-UCD

Other Names   :

Rialpha, B6.129X1-Prkar1atm1Gsm/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Prkar1atm1Gsm
Name: targeted mutation 1, G Stanley McKnight
Alteration at locus: Knockout
Gene Symbol: Prkar1a
Name: protein kinase, cAMP dependent regulatory, type I, alpha
Chromosome: 11
Alteration at locus: Knockout

Genetic Alterations:
A neo cassette was inserted into exon 3.

Genotype Determination:

ES Cell Line: REK3 derived from 129X1/SvJ

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

Phenotype

Homozygous phenotype: Homozygous mutants embryos fail to develop a functional heart tube at E8.5 and are resorbed at approximately E10.5.

Heterozygous phenotype: Heterozygous animals are prone to tumor formation and males have defective sperm and on high C57BL/6 background are severely subfertile.


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.
Prkar1atm1Gsm/Prkar1a+
        involves: 129X1/SvJ
  • cardiovascular system phenotype
    • decreased heart rate variability (MGI Ref ID J:93393)
      • depressed heart rate variability, however exhibit no heart rate changes, conduction delay or any cardiac myxomas
  • reproductive system phenotype
    • reduced male fertility (MGI Ref ID J:93393)
  • tumorigenesis
    • increased tumor incidence (MGI Ref ID J:93393)
      • increase in frequency of extracardiac tumors; 12 of 17 mutants developed tumors
      • hepatocellular carcinoma (MGI Ref ID J:93393)
        • 5 of 12 mutants that develop tumors have hepatocellular carcinomas
      • sarcoma (MGI Ref ID J:93393)
        • 3 of 12 mutants that develop tumors have soft tissue sarcomas with myxomatous differentiation invading the calvaria
        • 2 of 12 mutants that develop tumors have paraspinal and spinal sarcomas (chondro- and meningeal saracomas) with cord compression and lower limb paralysis
        • hemangiosarcoma (MGI Ref ID J:93393)
          • 4 of 12 mutants that develop tumors have hemangiosarcomas of the spleen with myxoid regions
          • splenic hemangiosarcomas are associated with metachronous lesions including colonic, ovarian, and pulmonary hemangiosarcomas
        • increased fibrosarcoma incidence (MGI Ref ID J:93393)
          • 2 of 12 mutants that develop tumors have s.c. soft tissue myxoid fibrosarcomas of the forelimb
  • pigmentation phenotype
    • pigmentation phenotype (MGI Ref ID J:93393)
      • pigmentation is normal
Prkar1atm1Gsm/Prkar1atm1Gsm
        involves: 129X1/SvJ * C57BL/6
  • mortality/aging
    • complete embryonic lethality during organogenesis (MGI Ref ID J:78010)
      • die between E10.5 and E11.5
  • growth/size phenotype
    • abnormal embryo size (MGI Ref ID J:78010)
      • greatly reduced trunk structure, however anterior-posterior axis is clearly apparent
      • decreased embryo size (MGI Ref ID J:78010)
        • smaller by E7.5
    • embryonic growth retardation (MGI Ref ID J:78010)
      • severe growth retardation with developmental delay
      • the E9.5 mutant embryo is similar in size to an E8 wild-type embryo
  • cardiovascular system phenotype
    • abnormal heart development (MGI Ref ID J:78010)
      • the cardiogenic plate, rather than being displaced more caudally by the formation of the heart tube, it is tightly juxtaposed to the prencephalon
      • abnormal heart tube morphology (MGI Ref ID J:78010)
        • heart tube does not form although a cardiogenic plate is present
  • embryogenesis phenotype
    • abnormal developmental patterning (MGI Ref ID J:78010)
      • abnormal axial mesoderm (MGI Ref ID J:78010)
        • axial mesoderm is greatly reduced in size
      • abnormal paraxial mesoderm (MGI Ref ID J:78010)
        • paraxial mesoderm is greatly reduced in size
      • abnormal primitive streak morphology (MGI Ref ID J:78010)
        • reduction in primitive streak mesoderm
        • exhibit aberrant and highly disorganized migration of mesodermal cells away from the primitive streak
        • about 1/3 the number of mesodermal cells exit the streak and move laterally and anteriorly, resulting in an accumulation of presumptive mesoderm beneath the primitive streak
      • failure of initiation of embryo turning (MGI Ref ID J:78010)
        • do not initiate the embryo turning process that occurs at the 7-8 somite transition
    • abnormal embryo size (MGI Ref ID J:78010)
      • greatly reduced trunk structure, however anterior-posterior axis is clearly apparent
      • decreased embryo size (MGI Ref ID J:78010)
        • smaller by E7.5
    • abnormal embryonic tissue morphology (MGI Ref ID J:78010)
      • mutant embryos have a flattened morphology by E7.5
      • abnormal axial mesoderm (MGI Ref ID J:78010)
        • axial mesoderm is greatly reduced in size
      • abnormal paraxial mesoderm (MGI Ref ID J:78010)
        • paraxial mesoderm is greatly reduced in size
      • abnorm al somite shape (MGI Ref ID J:78010)
        • somites are irregularly shaped at E9.5
      • abnormal somite size (MGI Ref ID J:78010)
        • somites are very small at E9.5
    • abnormal visceral yolk sac morphology (MGI Ref ID J:78010)
      • exhibit a ruffled yolk sac membrane by E7.5
    • embryonic growth retardation (MGI Ref ID J:78010)
      • severe growth retardation with developmental delay
      • the E9.5 mutant embryo is similar in size to an E8 wild-type embryo
  • cellular phenotype
    • abnormal cell content or morphology (MGI Ref ID J:78010)
      • mesodermal primary embryonic fibroblasts from E8.5 embryos have a flattened and box-shaped or rounded morphology with multiple actin organizing centers that extend in all directions rather than the typical spindled morphology with sparse parallel actin fibers
    • abnormal cell migration (MGI Ref ID J:78010)
      • mesodermal primary embryonic fibroblasts complete wound healing faster than wild-type fibroblasts

Strain of Origin: 129X1/SvJ

Strain genetic background: C57BL/6

Suggested Control Mice: Wild-type littermates

Research Applications

  • Cancer
  • Reproduction

Strain Origin

Donor: G. Stanley McKnight, Ph.D., University of Washington

Primary Reference:

  • Amieux PS, Howe DG, Knickerbocker H, Lee DC, Su T, Laszlo GS, Idzerda RL, McKnight GS. Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo. J Biol Chem. 2002 Jul 26;277(30):27294-304. Epub 2002 May 9. (Medline PMID: 12004056)
  • Veugelers M, Wilkes D, Burton K, McDermott DA, Song Y, Goldstein MM, La Perle K, Vaughan CJ, O'Hagan A, Bennett KR, Meyer BJ, Legius E, Karttunen M, Norio R, Kaariainen H, Lavyne M, Neau JP, Richter G, Kirali K, Farnsworth A, Stapleton K, Morelli P, Takanashi Y, Bamforth JS, Eitelberger F, Noszian I, Manfroi W, Powers J, Mochizuki Y, Imai T, Ko GT, Driscoll DA, Goldmuntz E, Edelberg JM, Collins A, Eccles D, Irvine AD, McKnight GS, Basson CT. Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice. Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14222-7. Epub 2004 Sep 15. (Medline PMID: 15371594)

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.

Onco-Mouse Patents. Canada: CA1341442 expires Oct. 7, 2020. US patents: 5,925,803 expires July 20, 2016 5,807,571 expired Feb. 11, 2009 4,736,866 expired April 12, 2005

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
000413-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
000413-UCD-OVARIESCryo-preserved ovarian tissue
$1,038.00
Non-Profit
Aliquot Approximate quantity3: 2-4 ovaries / 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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