Strain Detail Sheet

Strain Name    :

129S6-Cyp11b2tm2Unc/Mmnc

Stock Number :

030342-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Cyp11b2tm2Unc
Name: targeted mutation 2, University of North Carolina
Alteration at locus: Knockout
Gene Symbol: Cyp11b2
Name: cytochrome P450, family 11, subfamily b, polypeptide 2
Chromosome: 15
Alteration at locus: Knockout

Genetic Alterations:
The targeted replacement of the 3' untranslated region of Aldosterone Synthase gene (AS) with 4 copies of the bovine growth hormone 3'-UTR with its own GU/U rich element.

Genotype Determination:

  • The genotyping protocol for this strain is currently not available. The MMRRC will develop a protocol if this strain is ordered.

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: ~10mmHg higher blood pressure, higher plasma aldosterone, lower plasma potassium, greater renal expression of the the alpha subunit of epithelial sodium channel on high salt diet, increased cardiac hypertrophy and oxidative stress after angiotensin II infusion on high salt diet and resistance to the effects of low salt diet.

Heterozygous phenotype: not different from background strain


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Cyp11b2tm1Hsk/Cyp11b2tm1Hsk
        involves: 129S6/SvEvTac
  • mortality/aging
    • partial postnatal lethality (MGI Ref ID J:99269)
      • 30% die between day 7 and 28
  • growth/size phenotype
    • decreased body size (MGI Ref ID J:99269)
      • adults weight is 75% of wild-type
  • homeostasis/metabolism phenotype
    • abnormal enzyme/ coenzyme level (MGI Ref ID J:99269)
      • angiotensin II level is 4x wild-type
      • increased circulating renin level (MGI Ref ID J:99269)
        • mutant level is 45x wild-type
    • decreased circulating aldosterone level (MGI Ref ID J:99269)
      • aldosterone was undetected in mutants
    • decreased circulating chloride level (MGI Ref ID J:99269)
      • mutant tests 128.8 +/- 0.6 verses 133.1 +/- 0.6 mM in wild-type
    • increased circulating corticosterone level (MGI Ref ID J:99269)
      • mutant tests 79.0 +/- 11.0 verses 51.2 +/- 11.1 ng/ml in wild-type
    • increased circulating potassium level (MGI Ref ID J:99269)
      • mutant tests 6.1 +/- 0.1 verses 5.2+/- 0.1 mM in wild-type
    • increased renin activity (MGI Ref ID J:99269)
  • cardiovascular system phenotype
    • hypotension (MGI Ref ID J:99269)
      • mutant tests 111.7 verses 97.3 mM Hg in wild-type
  • endocrine/exocrine gland phenotype
    • abnormal adrenal cortex morphology (MGI Ref ID J:99269)
      • adrenal cortex is disorganized and glomerulosa is thickened
      • Oil-Red-O staining shows lipid levels are 3x wild-type
      • abnormal adrenocortical cell morphology (MGI Ref ID J:99269)
        • adrenal cortex cells appear foamy, and have a vacuolated cytoplasm and abnormal shapes
      • abnormal zona glomerulosa morphology (MGI Ref ID J:99269)
        • zona glomerulosa is widened and includes easily detectable renin-containing cells

Strain of Origin: 129S6/SvEvTac

Strain genetic background: mixed 129S6/SvEvTac and C57BL6/J

Strain Development: Always maintained on SvEv strain, and also backcross 2 of C57BL/6J

Suggested Control Mice:

  • Wildtype littermates

Research Applications

  • Cardiovascular
  • Diabetes/Obesity
  • Models for Human Disease

Strain Origin

Donor: Oliver Smithies, Ph.D., Univerisity of North Carolina

Primary Reference:

  • Makhanova N, Hagaman J, Kim HS, Smithies O. Salt-sensitive blood pressure in mice with increased expression of aldosterone synthase. Hypertension. 2008 Jan;51(1):134-40. Epub 2007 Nov 26. (Medline PMID: 18039983)
  • Makhanova N, Sequeira-Lopez ML, Gomez RA, Kim HS, Smithies O. Disturbed homeostasis in sodium-restricted mice heterozygous and homozygous for aldosterone synthase gene disruption. Hypertension. 2006 Dec;48(6):1151-9. Epub 2006 Oct 30. (Medline PMID: 17075030)
  • Lee G, Makhanova N, Caron K, Lopez ML, Gomez RA, Smithies O, Kim HS. Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice. Endocrinology. 2005 Jun;146(6):2650-6. Epub 2005 Feb 24. (Medline PMID: 15731365 )

Colony and Husbandry Information

Special Considerations

Donor states: "Mice are very characteristic of the normal 129 strain in breeding efficiency and performance. They are more susceptible to hypertension with a moderately high salt diet."

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_health@med.unc.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
030342-UNC-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
Litter Recovered litter1; additional fees for any special requests.
030342-UNC-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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