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Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Hemizygote (Female x Male) Species laboratory mouse Generation N10F1 (19-DEC-07) Donating Investigator IMR Colony, The Jackson Laboratory Description
Mice that are homozygous for this "MerCreMer" double fusion protein are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Cre expression in heart tissue is confirmed by western blot. Southern blot confirmed heart cell specificity compared to brain, kidney, lung, liver, and skeletal muscle. Insertion of this transgene and its protein show no changes in echocardiography, heart mass or pathology, or hypertrophy marker genes compared to nontransgenic littermates. Of note, this double fusion protein has substantially greater Cre recombinase activity with less promiscuity compared with a single CreMer fusion protein. As the cre is flanked on each end with a mutated murine estrogen receptor ligand binding domain (amino acids 281-599, G525R); Cre expression is tamoxifen inducible yet estrogen insensitive. Inducible expression of cre in cardiac cells makes this strain suitable for creating bitransgenic mice for use in studies of temporally regulated deletion of loxP-flanked targeted genes.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Development
A transgenic construct using the cardiac-specific murine alpha-myosin heavy chain promoter to direct expression of a double fusion protein was injected into FVB/N embryos. This double fusion protein, MerCreMer, has Cre recombinase gene flanked on each end with a mutated murine estrogen receptor ligand binding domain (amino acids 281-599, G525R); thus rendering cre expression tamoxifen inducible yet estrogen insensitive. These embryos were implanted into pseudopregnant FVB/N females. Founder animals were backcrossed to mice with a (B6 x 129/Sv)F1 genetic background for 15 generations and were subsequently backcrossed to C57BL/6J mice for 5 generations.
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Strains carrying Tg(Myh6-cre/Esr1)1Jmk allele
005650 B6129-Tg(Myh6-cre/Esr1)1Jmk/J View Strains carrying Tg(Myh6-cre/Esr1)1Jmk (1 strain)
Strains carrying other alleles of Esr1
006403 129S.B6-Tg(KRT14-Esr1/HRAS)1Pkha/J 004744 B6.129P2-Esr1tm1Ksk/J 004682 B6.Cg-Tg(CAG-cre/Esr1)5Amc/J 006774 FVB-Tg(Col2a1-cre/ESR1)KA3Smac/J 006822 FVB-Tg(KRT14-MAP2K1/Esr1)12Pkha/J 008464 STOCK Foxa2tm2.1(cre/Esr1)Moon/J 004453 STOCK Tg(CAG-cre/Esr1)5Amc/J 008122 STOCK Tg(Ins2-cre/Esr1)1Dam/J 005107 STOCK Tg(KRT14-cre/Esr1)20Efu/J 008119 STOCK Tg(Neurog3-cre/Esr1)1Dam/J View Strains carrying other alleles of Esr1 (10 strains)
Strains carrying other alleles of cre
View Strains carrying other alleles of cre (124 strains)
Congenic Nomenclature
Cre-lox Systems
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
cre relatedResearch Tools
Cardiovascular Research (Cre-lox System)
Cre-lox System (Cre-Recombinase Expression: Inducible)
Genetics Research (Mutagenesis and Transgenesis: Cre-lox System)
Genetics Research (Tissue/Cell Markers: Cre-lox System)
Research Tools
Cre-lox System
Genetics Research (Mutagenesis and Transgenesis: Cre-lox System)
| Allele Symbol | Tg(Myh6-cre/Esr1)1Jmk | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Jeffery D Molkentin | ||
| Allele Type | Transgenic (Cre/Flp) | ||
| Common Name(s) | MCM; MerCreMer; alpha-MHC-MerCreMer; mer; | ||
| Mutation Made By | Jeffery Molkentin, Children's Hospital Medical Center | ||
| Strain of Origin | FVB | ||
| Site of Expression | tamoxifen inducible (yet estrogen insensitive) Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer); expression in developing and adult heart | ||
| Expressed Gene | Esr1, estrogen receptor 1 (alpha), mouse, laboratory | ||
| Expressed Gene | cre, cre recombinase, bacteriophage P1 | ||
| Cre recombinase is an enzyme derived from the bacteriophage P1 that specifically recognizes loxP sites. Cre has been shown to effectively mediate the excision of DNA located between loxP sites. After the excision event, the DNA ends recombine leaving a single loxP site in place of the intervening sequence. | |||
| Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine | ||
| Molecular Note | This transgene expresses a cre recombinase/ mutant estrogen receptor ligand binding domain fusion protein under the control of a mouse cardiac-specific alpha-myosin heavy chain promoter. Expression was detected in the juvenile and adult heart, but the protein is inactive until induced with tamoxifen. [MGI Ref ID J:82027] | ||
Genotyping Protocols
Tg(cre/Esr1), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Sohal DS; Nghiem M; Crackower MA; Witt SA; Kimball TR; Tymitz KM; Penninger JM; Molkentin JD. 2001. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res 89(1):20-5. [PubMed: 11440973] [MGI Ref ID J:82027]
Tg(Myh6-cre/Esr1)1Jmk relatedChen X; Shevtsov SP; Hsich E; Cui L; Haq S; Aronovitz M; Kerkela R; Molkentin JD; Liao R; Salomon RN; Patten R; Force T. 2006. The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy. Mol Cell Biol 26(12):4462-73. [PubMed: 16738313] [MGI Ref ID J:109612]
Georges R; Nemer G; Morin M; Lefebvre C; Nemer M. 2008. Distinct expression and function of alternatively spliced Tbx5 isoforms in cell growth and differentiation. Mol Cell Biol 28(12):4052-67. [PubMed: 18391012] [MGI Ref ID J:137268]
Herrmann S; Stieber J; Stockl G; Hofmann F; Ludwig A. 2007. HCN4 provides a 'depolarization reserve' and is not required for heart rate acceleration in mice. EMBO J 26(21):4423-32. [PubMed: 17914461] [MGI Ref ID J:139560]
Kostetskii I; Li J; Xiong Y; Zhou R; Ferrari VA; Patel VV; Molkentin JD; Radice GL. 2005. Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96(3):346-54. [PubMed: 15662031] [MGI Ref ID J:98828]
Lavine KJ; Kovacs A; Ornitz DM. 2008. Hedgehog signaling is critical for maintenance of the adult coronary vasculature in mice. J Clin Invest 118(7):2404-14. [PubMed: 18568073] [MGI Ref ID J:137685]
Lavine KJ; White AC; Park C; Smith CS; Choi K; Long F; Hui CC; Ornitz DM. 2006. Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes Dev 20(12):1651-66. [PubMed: 16778080] [MGI Ref ID J:109722]
Li J; Levin MD; Xiong Y; Petrenko N; Patel VV; Radice GL. 2008. N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility. J Mol Cell Cardiol 44(3):597-606. [PubMed: 18201716] [MGI Ref ID J:133753]
Li J; Patel VV; Kostetskii I; Xiong Y; Chu AF; Jacobson JT; Yu C; Morley GE; Molkentin JD; Radice GL. 2005. Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis. Circ Res 97(5):474-81. [PubMed: 16100040] [MGI Ref ID J:112334]
Lisewski U; Shi Y; Wrackmeyer U; Fischer R; Chen C; Schirdewan A; Juttner R; Rathjen F; Poller W; Radke MH; Gotthardt M. 2008. The tight junction protein CAR regulates cardiac conduction and cell-cell communication. J Exp Med 205(10):2369-79. [PubMed: 18794341] [MGI Ref ID J:140109]
Moga MA; Nakamura T; Robbins J. 2008. Genetic approaches for changing the heart and dissecting complex syndromes. J Mol Cell Cardiol 45(2):148-55. [PubMed: 18601931] [MGI Ref ID J:139282]
Nakai A; Yamaguchi O; Takeda T; Higuchi Y; Hikoso S; Taniike M; Omiya S; Mizote I; Matsumura Y; Asahi M; Nishida K; Hori M; Mizushima N; Otsu K. 2007. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13(5):619-24. [PubMed: 17450150] [MGI Ref ID J:121778]
Parlakian A; Charvet C; Escoubet B; Mericskay M; Molkentin JD; Gary-Bobo G; De Windt LJ; Ludosky MA; Paulin D; Daegelen D; Tuil D; Li Z. 2005. Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart. Circulation 112(19):2930-9. [PubMed: 16260633] [MGI Ref ID J:135043]
Peng J; Raddatz K; Molkentin JD; Wu Y; Labeit S; Granzier H; Gotthardt M. 2007. Cardiac hypertrophy and reduced contractility in hearts deficient in the titin kinase region. Circulation 115(6):743-51. [PubMed: 17261657] [MGI Ref ID J:132331]
Petrich BG; Molkentin JD; Wang Y. 2003. Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination. FASEB J 17(6):749-51. [PubMed: 12594183] [MGI Ref ID J:128410]
Ruan H; Mitchell S; Vainoriene M; Lou Q; Xie LH; Ren S; Goldhaber JI; Wang Y. 2007. Gi alpha 1-mediated cardiac electrophysiological remodeling and arrhythmia in hypertrophic cardiomyopathy. Circulation 116(6):596-605. [PubMed: 17646583] [MGI Ref ID J:139853]
Sano M; Minamino T; Toko H; Miyauchi H; Orimo M; Qin Y; Akazawa H; Tateno K; Kayama Y; Harada M; Shimizu I; Asahara T; Hamada H; Tomita S; Molkentin JD; Zou Y; Komuro I. 2007. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446(7134):444-8. [PubMed: 17334357] [MGI Ref ID J:120332]
Syed F; Odley A; Hahn HS; Brunskill EW; Lynch RA; Marreez Y; Sanbe A; Robbins J; Dorn GW nd. 2004. Physiological growth synergizes with pathological genes in experimental cardiomyopathy. Circ Res 95(12):1200-6. [PubMed: 15539635] [MGI Ref ID J:133068]
Wang GS; Kearney DL; De Biasi M; Taffet G; Cooper TA. 2007. Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy. J Clin Invest 117(10):2802-11. [PubMed: 17823658] [MGI Ref ID J:127391]
Xiao R; Sun Y; Ding JH; Lin S; Rose DW; Rosenfeld MG; Fu XD; Li X. 2007. Splicing regulator SC35 is essential for genomic stability and cell proliferation during mammalian organogenesis. Mol Cell Biol 27(15):5393-402. [PubMed: 17526736] [MGI Ref ID J:123618]
Xiong D; Yajima T; Lim BK; Stenbit A; Dublin A; Dalton ND; Summers-Torres D; Molkentin JD; Duplain H; Wessely R; Chen J; Knowlton KU. 2007. Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy. Circulation 115(1):94-102. [PubMed: 17190866] [MGI Ref ID J:128060]
Zhong W; Mao S; Tobis S; Angelis E; Jordan MC; Roos KP; Fishbein MC; de Alboran IM; MacLellan WR. 2006. Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway. EMBO J 25(16):3869-79. [PubMed: 16902412] [MGI Ref ID J:119290]
Zhou J; Qu J; Yi XP; Graber K; Huber L; Wang X; Gerdes AM; Li F. 2007. Upregulation of gamma-catenin compensates for the loss of beta-catenin in adult cardiomyocytes. Am J Physiol Heart Circ Physiol 292(1):H270-6. [PubMed: 16936006] [MGI Ref ID J:119968]
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry Current colony is maintained by hemizygote X wildtype sibling (or reciprocal) crosses. Mating System +/+ sibling x Hemizygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Hemizygous for Tg(Myh6-cre/Esr1)1Jmk *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Hemizygous for Tg(Myh6-cre/Esr1)1Jmk x Noncarrier $288.65 Noncarrier x Hemizygous for Tg(Myh6-cre/Esr1)1Jmk
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Hemizygous for Tg(Myh6-cre/Esr1)1Jmk *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Hemizygous for Tg(Myh6-cre/Esr1)1Jmk x Noncarrier $375.30 Noncarrier x Hemizygous for Tg(Myh6-cre/Esr1)1Jmk
| Supply Notes |
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| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
For additional Licensing and Use Restrictions view the link(s) below:
- Notice Regarding cre/Esr1 (Tamoxifen Inducible Cre) Strains.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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