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Map2k1flox/flox/Map2k2-/- are viable and to do present any phenotype
Homozygous: Map2k1-/- mutants are embryonic lethal due to extraembryonic defects, while Map2k2-/- mutants are viable and fertile. Double-mutant Map2k1-/- Map2k2-/- mice die between E3.5 and E6.5. Conditional deletion of Map2k1 in a specific tissue in the Map2k2 null background generates a panoply of phenotype.
Heterozygous: Map2k1+/- and Map2k2+/- mice are viable and fertile. Ninety percent of the animals heterozygous for both alleles die during gestation, but surviving animals are viable and fertile.
Defects in the lungs, kidney, testis, skin, placenta, nervous system when both genes are deleted.
The Map2k1tm1Chrn allele was introduced with WW6 ES cells derived from STOCK 129/Sv and C57BL/6J and SJL; development detail for the Map2k1tm1Chrn is not available. Chimeras were crossed with "129Sv/Ev mice" (exact strain unknown) to establish germline transmission. Backcrossing information is unavailable. This line is, therefore, deemed STOCK.
Bissonauth V, Roy S, Gravel M, Guillemette S, and Charron J. Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis. Development. 2006 Sep;133(17):3429-40. Epub 2006 Aug 3. (Medline PMID: 16887817)
Scholl FA, Dumesic PA, Barragan DI, Harada K, Bissonauth V, Charron J, Khavari PA. Mek 1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell. 2007 Apr;12(4):615-29. (Medline PMID: 17419998)
Newbern J, Zhong J, Wickramasinghe RS, Li X, Wu Y, Samuels I, Cherosky N, Karlo JC, O'Loughlin B, Wilkenheiser J, Gargesha M, Doughman YQ, Charron J, Ginty DD, Watanabe M, Saitta SC, Snider WD, Landreth GE. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17115-20. Epub 2008 Oct 24. (Medline PMID: 18952847)
Nadeau V, Guillemette S, Belanger LF, Jacob O, Roy S, Charron J. Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development. 2009 Apr;136(8):1363-74. (Medline PMID: 19304888)
Scholl FA, Dumesic PA, Barragan DI, Charron J, Khavari PA. Mek 1/2 gene dosage determines tissue response to oncogenic Ras signaling in the skin. Oncogene. 2009 Mar 26;28(12):1485-95. Epub 2009 Feb 9. (Medline PMID: 19198628)
Scholl FA, Dumesic PA, Barragan DI, Harada K, Charron J, Khavari PA. Selective role for Mek1 but not Mek2 in the induction of epidermal neoplastia. Cancer Res. 2009 May 1;69(9):3772-8. Epub 2009 Apr 21. (Medline PMID: 19383924)
Yamashita S, Tai P, Charron J, Ko C, Ascoli M. The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility. Mol Endocrinol. 2011 Jul;25(7):1211-22. Epub 2011 Apr 28. (Medline PMID: 21527500)
Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J, Charron J, Snider WD. MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron. 2012 Sep 20;75(6):1035-50. (Medline PMID: 22998872)
Rastogi R, Jiang Z, Ahmad N, Rosati R, Liu Y, Beuret L, Monks R, Charron J, Birnbaum MJ, Samavati L. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase pathways. J Biol Chem. 2013 Nov 22;288(47):33966-77. Epub 2013 Oct 14. (Medline PMID: 24126911)
Shim JH, Greenblatt MB, Zou W, Huang Z, Wein MN, Brady N, Hu D, Charron J, Brodkin HR, Petsko GA, Zaller D, Zhai B, Gygi S, Glimcher LH, Jones DC. Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J Clin Invest. 2013 Sep;123(9):4010-22. Epub 2013 Aug 15. (Medline PMID: 23945236)
Whittington RA, Bretteville A, Virag L, Emala CW, Maurin TO, Marcouiller F, Julien C, Petry FR, El-Khoury NB, Morin F, Charron J, Planel E. Anesthesia-induced hypothermia mediates decreased ARC gene and protein expression through ERK/MAPK inactivation. Sci Rep. 2013;3:1388. (Medline PMID: 24045785)
Boucherat O, Nadeau V, Berube-Simard FA, Charron J, Jeannotte L. Crucial requirement of ERK/MAPK signaling in respiratory tract development. Development. 2014 Aug;141(16):3197-211. (Medline PMID: 25100655)
Ihermann-Hella A, Lume M, Miinalainen IJ, Pirttiniemi A, Gui Y, Peranen J, Charron J, Saarma M, Costantini F, Kuure S. Mitogen-activated protein kinase (MAPK) pathway regulates branching by remodeling epithelial cell adhesion. PLoS Genet. 2014 Mar 6;10(3):e1004193. (Medline PMID: 24603431)
Nadeau V, Charron J. Essential role of the ERK/MAPK pathway in blood-placental barrier formation. Development. 2014 Jul;141(14):2825-37. Epub 2014 Jun 19. (Medline PMID: 24948605)
O'Donovan KJ, Ma K, Guo H, Wang C, Sun F, Han SB, Kim H, Wong JK, Charron J, Zou H, Son YJ, He Z, Zhong J. B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. J Exp Med. 2014 May 5;211(5):801-14. Epub 2014 Apr 14. (Medline PMID: 24733831)
Bouhamdan M, Bauerfeld C, Talreja J, Beuret L, Charron J, Samavati L. MEK1 dependent and independent ERK activation regulates IL-10 and IL-12 production in bone marrow derived macrophages. Cell Signal. 2015 Oct;27(10):2068-76. Epub 2015 Jul 21. (Medline PMID: 26208884)
Noel A, Poitras I, Julien J, Petry FR, Morin F, Charron J, Planel E. ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro. Neurobiol Aging. 2015 Feb;36(2):901-2. Epub 2014 Nov 14. (Medline PMID: 25491074)
Aoidi R, Maltais A, Charron J. Functional Redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect. Sci Signal. 2016 Jan 26;9(412):ra9. (Medline PMID: 26814233)
Colony Surveillance Program and Current Health Reports
>15
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.