Strain Name:

STOCK Hcn4tm2.1(cre/ERT2)Sev/J

Stock Number:

024283

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
Common Names: HCN4CreERT2;    
HCN4CreERT2 mice express CreERT2 in the first heart field of differentiating myocytes in the developing cardiac crescent.

Description

Strain Information

Type Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemWild-type x Heterozygote         (Female x Male)   21-MAR-14
Mating SystemHeterozygote x Wild-type         (Female x Male)   21-MAR-14
Specieslaboratory mouse
Generation?+pN1 (02-JUN-14)
Generation Definitions
 
Donating Investigator Sylvia Evans,   University of California, San Diego

Description
Heterozygous mice are viable and fertile, homozygotes are embryonic lethal. The HCN4CreERT2 allele expresses CreERT2 from the hyperpolarization-activated, cyclic nucleotide-gated K+ 4 (HCN4) promoter/enhancer elements. HCN4 is expressed in the first heart field of differentiating myocytes in the developing cardiac crescent. Cre-ERT2 fusion gene activity is observed in the same cells only following tamoxifen administration. When these mice are bred with mice containing loxP-flanked sequence, Cre-mediated recombination will result in deletion of the floxed sequences in the cardiac conduction system (CCS) of the offspring.

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

Development
A targeting vector was designed to insert a CreERT2 coding sequence and frt-flanked neomycin resistance selection cassette immediately before endogenous start codon of hyperpolarization-activated, cyclic nucleotide-gated K+ 4 (HCN4) gene. This construct was electroporated into embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred. Mice were bred to Flp-transgenic mice on a Black Swiss background to remove the neo cassette, and progeny were crossed to remove the Flp transgene. These mice were maintained on a Black Swiss outbred background. Upon arrival at The Jackson Laboratory, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Hcn4
008780   B6.Cg-Hcn4tm1Rsei/J
024284   STOCK Hcn4tm3Sev/J
View Strains carrying other alleles of Hcn4     (2 strains)

Strains carrying other alleles of cre/ERT2
017611   129-Mcm2tm1(cre/ERT2)Scpr/J
009575   B6(129S4)-Et(cre/ERT2)119Rdav/J
009580   B6(129S4)-Et(cre/ERT2)1382Rdav/J
012688   B6(129S4)-Et(cre/ERT2)13866Rdav/J
009581   B6(129S4)-Et(cre/ERT2)1642Rdav/J
009582   B6(129S4)-Et(cre/ERT2)1645Rdav/J
009583   B6(129S4)-Et(cre/ERT2)1957Rdav/J
009584   B6(129S4)-Et(cre/ERT2)2007Rdav/J
009585   B6(129S4)-Et(cre/ERT2)2047Rdav/J
009574   B6(129S4)-Et(cre/ERT2)21Rdav/J
009577   B6(129S4)-Et(cre/ERT2)296Rdav/J
009578   B6(129S4)-Et(cre/ERT2)398Rdav/J
009573   B6(129S4)-Et(cre/ERT2)4Rdav/J
010688   B6(129S4)-Et(cre/ERT2)6691Rdav/J
010689   B6(129S4)-Et(cre/ERT2)6959Rdav/J
010690   B6(129S4)-Et(cre/ERT2)7089Rdav/J
010691   B6(129S4)-Et(cre/ERT2)7149Rdav/J
010692   B6(129S4)-Et(cre/ERT2)7381Rdav/J
010693   B6(129S4)-Et(cre/ERT2)8120Rdav/J
010694   B6(129S4)-Et(cre/ERT2)8131Rdav/J
009579   B6(129S4)-Et(cre/ERT2)837Rdav/J
010695   B6(129S4)-Et(cre/ERT2)9699Rdav/J
010696   B6(129S4)-Et(icre/ERT2)10596Rdav/J
010697   B6(129S4)-Et(icre/ERT2)10727Rdav/J
012689   B6(129S4)-Et(icre/ERT2)14163Rdav/J
012690   B6(129S4)-Et(icre/ERT2)14208Rdav/J
012694   B6(129S4)-Et(icre/ERT2)14915Rdav/J
022356   B6(129X1)-Tg(Cd4-cre/ERT2)11Gnri/J
013730   B6(Cg)-Calb2tm2.1(cre/ERT2)Zjh/J
010705   B6(Cg)-Dlx5tm1(cre/ERT2)Zjh/J
013048   B6(Cg)-Etv1tm1.1(cre/ERT2)Zjh/J
010776   B6(Cg)-Lhx6tm1(cre/ERT2)Zjh/J
010777   B6(Cg)-Pvalbtm1(cre/ERT2)Zjh/J
010708   B6(Cg)-Ssttm1(cre/ERT2)Zjh/J
026512   B6(Cg)-Tg(TPO-cre/ERT2)1139Tyj/J
021881   B6.129(Cg)-Arctm1.1(cre/ERT2)Luo/J
018867   B6.129(Cg)-Axin2tm1(cre/ERT2)Rnu/J
021882   B6.129(Cg)-Fostm1.1(cre/ERT2)Luo/J
008463   B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J
020940   B6.129P2(C)-Cx3cr1tm2.1(cre/ERT2)Jung/J
021160   B6.129P2(Cg)-Cx3cr1tm2.1(cre/ERT)Litt/WganJ
027116   B6.129P2-Cd19tm1(cre/ERT2)Rsky/J
008875   B6.129P2-Lgr5tm1(cre/ERT2)Cle/J
016934   B6.129P2-Lgr6tm2.1(cre/ERT2)Cle/J
016222   B6.129S(Cg)-Id2tm1.1(cre/ERT2)Blh/ZhuJ
005623   B6.129S6-Shhtm2(cre/ERT2)Cjt/J
019148   B6.Cg-Acantm1(cre/ERT2)Crm/J
012360   B6.Cg-Erbb4tm1.1(cre/ERT2)Aibs/J
023676   B6.Cg-Hprttm331(Ple275-icre/ERT2)Ems/Mmjax
023677   B6.Cg-Hprttm332(Ple272-icre/ERT2)Ems/Mmjax
023678   B6.Cg-Hprttm333(Ple281-icre/ERT2)Ems/Mmjax
023679   B6.Cg-Hprttm334(Ple279-icre/ERT2)Ems/Mmjax
023680   B6.Cg-Hprttm335(Ple277-icre/ERT2)Ems/Mmjax
023681   B6.Cg-Hprttm336(Ple134-icre/ERT2)Ems/Mmjax
023682   B6.Cg-Hprttm337(Ple285-icre/ERT2)Ems/Mmjax
023683   B6.Cg-Hprttm338(Ple284-icre/ERT2)Ems/Mmjax
023684   B6.Cg-Hprttm339(Ple280-icre/ERT2)Ems/Mmjax
023685   B6.Cg-Hprttm340(Ple252-icre/ERT2)Ems/Mmjax
023686   B6.Cg-Hprttm341(Ple273-icre/ERT2)Ems/Mmjax
023687   B6.Cg-Hprttm342(Ple282-icre/ERT2)Ems/Mmjax
023688   B6.Cg-Hprttm343(Ple270-icre/ERT2)Ems/Mmjax
023689   B6.Cg-Hprttm344(Ple5-icre/ERT2)Ems/Mmjax
023690   B6.Cg-Hprttm345(icre/ERT2)Ems/Mmjax
023691   B6.Cg-Hprttm346(Ple264-icre/ERT2)Ems/Mmjax
023692   B6.Cg-Hprttm347(Ple155-icre/ERT2)Ems/Mmjax
023693   B6.Cg-Hprttm348(Ple265-icre/ERT2)Ems/Mmjax
023694   B6.Cg-Hprttm349(Ple293-icre/ERT2)Ems/Mmjax
023695   B6.Cg-Hprttm350(Ple232-icre/ERT2)Ems/Mmjax
023696   B6.Cg-Hprttm351(Ple198-icre/ERT2)Ems/Mmjax
023697   B6.Cg-Hprttm352(Ple291-icre/ERT2)Ems/Mmjax
022861   B6.Cg-Nxph4tm1.1(cre/ERT2)Hze/J
017763   B6.Cg-Pax7tm1(cre/ERT2)Gaka/J
022862   B6.Cg-Penktm1.1(cre/ERT2)Hze/J
021189   B6.Cg-Pvalbtm1.1(cre/ERT2)Hze/J
022865   B6.Cg-Trib2tm1.1(cre/ERT2)Hze/J
022357   B6.Cg-Tg(Arc-cre/ERT2)MRhn/CdnyJ
026516   B6.Cg-Tg(Avil-cre/ERT2)AJwo/J
022390   B6.Cg-Tg(CDX2-Cre/ERT2)752Erf/J
016241   B6.Cg-Tg(Col1a1-cre/ERT2)1Crm/J
024709   B6.Cg-Tg(Ins1-cre/ERT)1Lphi/J
007606   B6.Cg-Tg(Thy1-cre/ERT2,-EYFP)AGfng/J
019079   B6.FVB-Tg(Myh11-cre/ERT2)1Soff/J
021961   B6;129-Abcg2tm3.1(cre/ERT2)Bsor/J
010531   B6;129-Bmi1tm1(cre/ERT)Mrc/J
012476   B6;129-Pax7tm2.1(cre/ERT2)Fan/J
009600   B6;129-Six2tm3(EGFP/cre/ERT2)Amc/J
010985   B6;129P-Klf3tm1(cre/ERT2)Pzg/J
015854   B6;129P2-Foxl2tm1(GFP/cre/ERT2)Pzg/J
014541   B6;129S-Nos1tm1.1(cre/ERT2)Zjh/J
010987   B6;129S-Sox18tm1(GFP/cre/ERT2)Pzg/J
017593   B6;129S-Sox2tm1(cre/ERT2)Hoch/J
014551   B6;129S4-Dlx1tm1(cre/ERT2)Zjh/J
012464   B6;129S4-Foxd1tm2(GFP/cre/ERT2)Amc/J
009576   B6;129S4-Et(cre/ERT2)278Rdav/J
024948   B6;129S6-Gdnftm1(cre/ERT2)Cos/J
012362   B6;129S6-Tg(Camk2a-cre/ERT2)1Aibs/J
017495   B6;129S7-Crim1tm1(GFP/cre/ERT2)Pzg/J
014638   B6;129X1-Cldn6tm1(cre/ERT2)Dam/J
018937   B6;C-Tg(Erv4-cre/ERT2*)657Slp/J
025809   B6;CBA-Tg(Fgfr3-icre/ERT2)4-2Wdr/J
025808   B6;CBA-Tg(Nkx2-1-cre/ERT2)1Kess/J
024768   B6;CBA-Tg(Upk2-icre/ERT2)1Ccc/J
017496   B6;D-Tg(Lfng-TagRFP/cre/ERT2)8Amc/J
018682   B6;D-Tg(Meox1-TagRFP/cre/ERT2)30Amc/J
018683   B6;D-Tg(Wnt11-TagRFP/cre/ERT2)28Amc/J
007610   B6;SJL-Tg(Thy1-cre/ERT2,-EYFP)VGfng/J
010550   B6N.FVB-Tg(Penk-glc-2-cre/ERT2)2And/J
017743   B6N;129S-Prom1tm1(cre/ERT2)Gilb/J
025124   C57BL/6-Tg(Adipoq-cre/ERT2)1Soff/J
025867   C57BL/6J-Tg(Neurod1-cre/ERT2)M1Fcal/J
024760   FVB/N-Tg(Ddx4-cre/ERT2)1Dcas/J
012882   STOCK Ascl1tm1.1(Cre/ERT2)Jejo/J
012710   STOCK Ccktm2.1(cre/ERT2)Zjh/J
007924   STOCK En2tm4(cre/ERT2)Alj/J
016961   STOCK Foxp3tm9(EGFP/cre/ERT2)Ayr/J
010702   STOCK Gad2tm1(cre/ERT2)Zjh/J
022135   STOCK Gbx2tm1.1(cre/ERT2)Jyhl/J
007913   STOCK Gli1tm3(cre/ERT2)Alj/J
017606   STOCK Hopxtm2.1(cre/ERT2)Joe/J
018418   STOCK Lrig1tm1.1(cre/ERT2)Rjc/J
014552   STOCK Nkx2-1tm1.1(cre/ERT2)Zjh/J
017536   STOCK Nkx6-2tm1(cre/ERT2)Fsh/J
009061   STOCK Osr1tm1(EGFP/cre/ERT2)Amc/J
017569   STOCK Polr2atm1(cre/ERT2)Bbd E4f1tm1.1Llca/J
017585   STOCK Polr2atm1(cre/ERT2)Bbd/J
022757   STOCK Prg4tm1(GFP/cre/ERT2)Abl/J
010912   STOCK Wt1tm2(cre/ERT2)Wtp/J
012691   STOCK Et(icre/ERT2)14374Rdav/J
012692   STOCK Et(icre/ERT2)14602Rdav/J
012693   STOCK Et(icre/ERT2)14624Rdav/J
008861   STOCK Tg(Ela1-Cre/ERT2)1Stof/J
022763   STOCK Tg(Eno2-cre/ERT2)1Pohlk/J
027681   STOCK Tg(Hnf1b-cre/ERT2)1Jfer/J
019380   STOCK Tg(IVL-cre/ERT2)1Blpn/J
017948   STOCK Tg(KRT18-cre/ERT2)23Blpn/J
017947   STOCK Tg(Krt8-cre/ERT2)17Blpn/J
018829   STOCK Tg(Sox9-cre/ERT2)1Msan/J
025520   STOCK Tg(T-cre/ERT2)1Lwd/J
View Strains carrying other alleles of cre/ERT2     (138 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Brugada Syndrome 8; BRGDA8   (HCN4)
Sick Sinus Syndrome 2, Autosomal Dominant; SSS2   (HCN4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Hcn4tm2.1(cre/ERT2)Sev/Hcn4tm2.1(cre/ERT2)Sev

        involves: Black Swiss * C57BL/6J
  • mortality/aging
  • complete embryonic lethality   (MGI Ref ID J:101977)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cardiovascular Research
Heart Abnormalities

Developmental Biology Research
Internal/Organ Defects
      heart

Internal/Organ Research
Heart Abnormalities

Research Tools
Cre-lox System
      Cre Recombinase Expression: Inducible

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Hcn4tm2.1(cre/ERT2)Sev
Allele Name targeted mutation 2.1, Sylvia Evans
Allele Type Targeted (Inducible, cre- or Flp-expressing)
Common Name(s) HCN4CreERT2;
Site of ExpressionMice carrying this allele express CreERT2 in the first heart field of differentiating myocytes in the developing cardiac crescent.
Expressed Gene cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene,
Gene Symbol and Name Hcn4, hyperpolarization-activated, cyclic nucleotide-gated K+ 4
Chromosome 9
Gene Common Name(s) SSS2;
Driver Note Hcn4
Inducible Note induced by tamoxifen
Molecular Note A targeting vector was designed to insert a CreERT2 coding sequence and frt-flanked neomycin resistance selection cassette immediately before endogenous start codon. The neo cassette was removed by FLP mediated recombination. [MGI Ref ID J:204126]
 

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cre Melt Curve Analysis, Probe
Generic Cre/ERT2 alternate1, MELT
Isl1tm1(cre)Sev, SEPARATED MELT


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liang X; Wang G; Lin L; Lowe J; Zhang Q; Bu L; Chen Y; Chen J; Sun Y; Evans SM. 2013. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res 113(4):399-407. [PubMed: 23743334]  [MGI Ref ID J:204126]

Additional References

Hcn4tm2.1(cre/ERT2)Sev related

The Jackson Laboratory. 2005. Information obtained from The Jackson Laboratory, Bar Harbor, ME Unpublished :.  [MGI Ref ID J:101977]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred to wildtype (noncarrier) mice from the colony. Homozygotes are embryonic lethal.
Mating SystemWild-type x Heterozygote         (Female x Male)   21-MAR-14
Heterozygote x Wild-type         (Female x Male)   21-MAR-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $246.90Female or MaleHeterozygous for Hcn4tm2.1(cre/ERT2)Sev  
Price per Pair (US dollars $)Pair Genotype
$320.90Heterozygous for Hcn4tm2.1(cre/ERT2)Sev x Wild-type for Hcn4tm2.1(cre/ERT2)Sev  
$320.90Wild-type for Hcn4tm2.1(cre/ERT2)Sev x Heterozygous for Hcn4tm2.1(cre/ERT2)Sev  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $321.00Female or MaleHeterozygous for Hcn4tm2.1(cre/ERT2)Sev  
Price per Pair (US dollars $)Pair Genotype
$417.20Heterozygous for Hcn4tm2.1(cre/ERT2)Sev x Wild-type for Hcn4tm2.1(cre/ERT2)Sev  
$417.20Wild-type for Hcn4tm2.1(cre/ERT2)Sev x Heterozygous for Hcn4tm2.1(cre/ERT2)Sev  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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Tel: 1-800-422-6423 or 1-207-288-5845
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Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Mice are subject to US Patent 6040430.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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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.

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