About   Help   FAQ
Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Hcn4tm1(cre/ERT2)Anlu
targeted mutation 1, Andreas Ludwig
MGI:3809312
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
ht1
Hcn4tm1(cre/ERT2)Anlu/Hcn4+ Not Specified MGI:3809393
cn2
Hcn4tm1Jsr/Hcn4tm1(cre/ERT2)Anlu involves: 129S1/Sv * 129X1/SvJ MGI:3809392
cn3
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Hcn4tm1(cre/ERT2)Anlu/Hcn4+
involves: 129S/SvEv MGI:5432113


Genotype
MGI:3809393
ht1
Allelic
Composition
Hcn4tm1(cre/ERT2)Anlu/Hcn4+
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hcn4tm1(cre/ERT2)Anlu mutation (0 available); any Hcn4 mutation (67 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
N
• tamoxifen treated mice exhibit normal modulation of heart rate

normal phenotype
• tamoxifen treated mice are indistinguishable from wild-type mice




Genotype
MGI:3809392
cn2
Allelic
Composition
Hcn4tm1Jsr/Hcn4tm1(cre/ERT2)Anlu
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hcn4tm1(cre/ERT2)Anlu mutation (0 available); any Hcn4 mutation (67 available)
Hcn4tm1Jsr mutation (0 available); any Hcn4 mutation (67 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• tamoxifen treated mice exhibit a more reduced heart rate in response to carbachol and adenosine A1-agonist CCPA compared to in similarly treated wild-type mice
• following tamoxifen treatment, mice exhibit reduced hyperpolarization-activated current (If) density and faster activation kinetics of the residual current compared to in wild-type mice
• however, residual hyperpolarization-activated current (If) is normally blocked by cesium
• following tamoxifen treatment, mice exhibit frequent sinus pauses in an otherwise normal electrocardiogram
• following tamoxifen treatment, 6 out of 11 sinoatrial nodes exhibit altered action potentials with membrane potentials that drift to hyperpolarization and cessation of discharge




Genotype
MGI:5432113
cn3
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Hcn4tm1(cre/ERT2)Anlu/Hcn4+
Genetic
Background
involves: 129S/SvEv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (2 available); any Gt(ROSA)26Sor mutation (993 available)
Hcn4tm1(cre/ERT2)Anlu mutation (0 available); any Hcn4 mutation (67 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• approximately 20% of mice die suddenly with no ante-mortem indication of illness within 60 days after high dose tamoxifen treatment

cardiovascular system
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose
• tamoxifen induced ablation of sinoatrial node cells is accompanied by a destructive fibrosis of nodal tissue
• following 5 days of tamoxifen treatment show alternating periods of slow and fast frequencies in R-R tachograms
• alterations of long electrical standstills (sinus pauses) and intermittent rapid atrial activity following tamoxifen treatment
• following 5 days of tamoxifen treatment absolute value of the maximally (isoprenaline) stimulated heart rate remained low
• following 5 days of high or low dose tamoxifen treatment heart rate falls by about 40 - 50% or 12%, respectively
• variety of cardiac rhythm disturbances; including sino-atrial arrhythmia, sino-atrial pause and to a minor extent supraventricular or ventricular tachycardia, following tamoxifen treatment
• complete heart block some weeks after tamoxifen treatment
• following tamoxifen treatment
• progressive prolongation of the P-R interval tends to result in complete isolated contraction of atria and ventricles with high dose tamoxifen treatment

muscle
• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
sick sinus syndrome DOID:13884 OMIM:163800
OMIM:608567
J:186021





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources
Funding Information
Warranty Disclaimer, Privacy Notice, Licensing, & Copyright
Send questions and comments to User Support.
last database update
12/10/2024
MGI 6.24
The Jackson Laboratory