Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart
J. Clin. Invest. Byung-Kwan Lim, et al. 118:2758 doi:10.1172/JCI34777 [
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Figure 3First-degree AV block in global CAR-KO embryos. (
A) Generation of global
CAR-deficient mice by gene targeting. Exon (E) 2 of
CAR was deleted and replaced with a β-galactosidase–neomycin cassette (β-Gal/Neo). B, BglII. (
B) Homologous recombination was confirmed by Southern bolt analysis using genomic DNA digested with NheI from selected ES cells. WT (+/+); heterozygous (+/–). (
C) Genotype of the embryos was confirmed by Southern blot analysis on DNA isolated from embryo yolk sacs (left panel). CAR expression was determined using immunoblot analysis of embryos (right panel) of heterozygous, homozygous-deficient (–/–), and WT mice. (
D) AV block in global CAR-KO mouse embryos was demonstrated by Doppler analysis of mitral inflow during the period of early rapid filling (E), atrial filling (A), and aortic outflow (OF). The PR intervals were calculated using the time from the beginning of the A-wave to the beginning of the aortic outflow. Mean PR intervals and heart rate in
CAR+/+ (
n = 8),
CAR+/– (
n = 9) and in
CAR–/– (
n = 8) embryos are shown (lower panel). Mean ± SD. *
P < 0.001.