These Kcnj12 knock-out mice exhibit an absence of inwardly rectifying potassium ion currents in cardiac ventribular myocytes, and altered electrocardiogram profiles are indicative of reduced heart rate and bradycardia.
Thomas Schwarz, Harvard University
Mice that are homozygous for the targeted mutation have a complete cleft of the secondary palate and die within 12 hours of birth. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by Northern blot analysis of cardiac tissue or Southern blot analysis. Inwardly rectifying potassium ion currents are absent in cerebral artery myocytes and cardiac ventribular myocytes isolated from homozygote neonates. Elevated external potassium ion concentrations do not dilate isolated neonatal cerebral arteries. Homozygotes exhibit altered electrocardiogram profiles indicative of reduced heart rate and bradycardia. This mutant mouse strain may be useful in studies of potassium ion dependent vasodilation, cardiac arrythmia such as Anderson syndrome, cleft palate and developmental bone malformation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire open reading frame. The construct was electroporated into 129-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Thomas L Schwarz|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcnj2, potassium inwardly-rectifying channel, subfamily J, member 2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||The entire open reading frame of the endogenous gene was replaced with a neomycin selection cassette.|
|Mutations Made By|| |
Joshua Zaritsky, Harvard University
The resulting chimeric animals were crossed to FVB mice, and then backcrossed to the same for 10 generations. The strain is maintained as a heterozygote due to neonatal homozygous lethality.
When using the Kir2.1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005057 in your Materials and Methods section.