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A conditionally excisable transcriptional stop codon (lox-3x stop-FRT-Neo-FRT-lox) and single missense point mutation (Q61R - p.Gln61Arg) were placed in the endogenous Nras locus using standard homologous recombination procedures. The Neo cassette was removed using mating to FlpE mice, followed by 7 backcrosses to C57BL/6J mice from Jackson labs. The resulting mice were then crossed to mice containing tyrosinase-ERT2 Cre (PMID:16676322) and floxed p16INK4a alleles. The current mice no longer have the floxed p16INK4a allele, just the LSL-NrasQ61R and tyrosinase-ERT2 Cre alleles.
HGVS nomenclature:
Homozygous: No defects in development or fertility observed.
Hetero/Hemizygous: No defects in development or fertility observed.
Cre-excised Phenotype: When treated topically with 4-hydroxytamoxifen to induce melanocyte-specific CRE activation, these mice spontaneously develop cutaneous melanoma. Otherwise, the mice appear phenotypically normal to wild-type C57BL6/J.
Burd CE, Liu W, Huynh MV, Waqas MA, Gillahan JE, Clark KS, Fu K, Martin BL,Jeck WR, Souroullas GP, Darr DB, Zedek DC, Miley MJ, Baguley BC, Campbell SL,Sharpless NE. Mutation-specific RAS oncogenicity explains NRAS codon 61 selectionin melanoma. Cancer Discov. 2014 Dec;4(12):1418-29. doi:10.1158/2159-8290.CD-14-0729. Epub 2014 Sep 24. (Medline PMID: 25252692)
Bosenberg M, Muthusamy V, Curley DP, Wang Z, Hobbs C, Nelson B, Nogueira C,Horner JW 2nd, Depinho R, Chin L. Characterization of melanocyte-specificinducible Cre recombinase transgenic mice. Genesis. 2006 May;44(5):262-7. (Medline PMID: 16676322)
Colony Surveillance Program and Current Health Reports
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.
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.
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.
1 The distribution fee covers the expense of rederiving mice from a live mouse; 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 contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 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.
4 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.