Strain Detail Sheet

Strain Name    :

B6;129-Gt(ROSA)26Sortm3(NOTCH3*R1031C)SatMmjax

Stock Number :

032999-JAX

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Target: Gt(ROSA)26Sortm3(NOTCH3*R1031C)Sat
Name: targeted mutation 3, Spyros Artavanis-Tsakonas
Alteration at locus: Knock-In
Target: Gt(ROSA)26Sor
Name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Alteration at locus: Knock-In
Target: NOTCH3 (Human)
Name: notch 3
Alteration at locus: Knock-In

Genetic Alterations:

Genotype Determination:

ES Cell Line: J1

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

Phenotype

Homozygotes: Homozygous ROSA NOTCH3-1031 mice are viable, fertile, with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-associated R1031C mutation inserted into the Gt(ROSA)26Sor locus. Expression of the mutated human NOTCH3 is blocked by an upstream loxP-flanked STOP sequence. When bred to cre expressing mice, the STOP sequence is deleted in the tissues of offspring where Cre recombinase is present, resulting in mutated human NOTCH3 expression and the parallel expression of enhanced green fluorescent protein (GFP) targeted to the nucleus. Expression in vascular smooth muscle cells is characterized by the pathological changes characteristic of CADASIL including cell degeneration and the presence of granular osmiophilic deposits. These mice allow inducible expression of a human mutation associated with ischemic stroke.

Heterozygote: Not evaluated

Strain of Origin: 129S6/SvEvTac

Strain genetic background: 129S

Strain Development: A targeting vector was designed with a splice acceptor site, a loxP-flanked PGK neomycin cassette, a human NOTCH3 cDNA encoding a CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)-associated mutation and an IRES-nuclear EGFP sequence was inserted into the GT(ROSA)26Sor locus. The CADASIL mutation is an amino acid substitution from arginine to cysteine at amino acid 1031 (R1031C). The construct was introduced into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting "1031" chimeric animals were crossed to 129S2/SvEv mice. The mice were crossed to 129S2/SvEv for an unknown number of generations and at some point to C57BL/6 mice. Upon arrival, mice were bred to 129S1/SvImJ for at least 1 generation to establish the colony.

Suggested Control Mice: Wild-type littermates

Research Applications

  • Apoptosis
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Immunology and Inflammation
  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor: Spyros Artavanis-Tsakonas, Ph.D., Harvard Medical School

Primary Reference:

  • Arboleda-Velasquez JF; Manent J; Lee JH; Tikka S; Ospina C; Vanderburg CR; Frosch MP; Rodriguez-Falcon M; Villen J; Gygi S; Lopera F; Kalimo H; Moskowitz MA; Ayata C; Louvi A; Artavanis-Tsakonas S, PNAS Plus: Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease., Proc Natl Acad Sci U S A 2011 May 24;108(21):E128-35 (Medline PMID: 21555590)
  • Arboleda-Velasquez JF, Lopera F, Lopez E, Frosch MP, Sepulveda-Falla D, Gutierrez JE, Vargas S, Medina M, Martinez De Arrieta C, Lebo RV, Slaugenhaupt SA, Betensky RA, Villegas A, Arcos-Burgos M, Rivera D, Restrepo JC, Kosik KS. C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke. Neurology. 2002 Jul 23;59(2):277-9. (Medline PMID: 12136071)

Colony and Husbandry Information

Special Considerations

While maintaining a live colony, these mice are bred as homozygotes.

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 csmmrrc@jax.org.

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
032999-JAX-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
032999-JAX-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

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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