Conditional miR-34afl/fl floxed mutant mice may have applications in studies related to the regulatory control of p53 pathways.
Andrea Ventura, Memorial Sloan Kettering Cancer Center
The miR-34 family of miRNAs (miR-34a, miR-34b, and miR-34c) are expressed mainly in the testis, brain, and lung. miR-34 proteins are induced upon p53 activation and are associated with tumor suppression, aging, neurodegeneration, and spermatogenesis. miR-34afl/fl mice possess loxP sites flanking the entire microRNA 34a (miR-34a) sequence. Homozygous miR-34afl/fl mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have miR-34a sequence deleted in the cre-expressing tissues. When crossed to mice expressing CAG-cre, miR-34a-/- mice exhibit abnormal neuronal precursor proliferation. When cre recombined miR-34a-/- mice are bred to Mirc21-/- mice (Stock No. 018546), which are deficient in miR-34b and miR-34c, the double mutant mice lack all three miR-34 family members. These miR-34 KO mice show normal development with an intact p53 pathway.
A targeting vector was designed to insert a loxP site upstream of the pre- microRNA 34a (miR-34a) sequence, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of the pre-miR-34a sequence. The construct was electroporated into (C57BL/6 x 129S4/SvJae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to Tg(ACTFLPe)9205Dym transgenic mice on a B6 background to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, resulting in a colony of miR-34afl/fl mice. These mice were maintained on mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.2, Andrea Ventura|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||targeted mutation 1.2, Andrea Ventura; Mir34atm1.2Aven|
|Gene Symbol and Name||Mir34a, microRNA 34a|
|Gene Synonym(s)||Mirn34a; mir 34a; Mirn34a; mmu-mir-34a; mir-34; miRNA34A; mir-34a|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|Molecular Note||A targeting vector was designed to insert a loxP site upstream of the sequence, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of the sequence. Flp-mediated recombination removed the neo cassette and left the sequence floxed.|
|Mutations Made By|| |
Andrea Ventura, Memorial Sloan Kettering Cancer Center
When maintaining a live colony, homozygous mice may be bred together.
When using the miR-34afl mouse strain in a publication, please cite the originating article(s) and include JAX stock #018545 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.