cardiovascular system
• 8-week old mice have a clear decrease in ZO-1 localized to the intercalated disc
• intercalated discs are punctuated by areas where there is an increase in the space between cardiac myocytes, usually near the adherens junctions
• disorganization of the electron-dense structures associated with the intercalated disc is observed
• disorganization of the myofilaments that attach to the intercalated disc also occurs
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• cardiac fibrosis occurs in mice 25 weeks of age
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• there is a progressive decrease in fractional shortening at 21 and 25 weeks of age
• fractional shortening degrades from a normal level at 17 weeks of age to half that of wild-type by 25 weeks of age
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• the R-to-R intervals are shorter in these mice with 127.3 ms in wild-type mice vs. 97.4 ms in mutant mice
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• AV-node block occurs in these mice with half the mice having a complete AV block and the other half having first-degree AV block over 90% of the time
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• in mice without complete AV blockage, there is an extended PR interval
• mean PR interval is 36.5 ms in wild-type compared with 53.9 ms in mutant mice
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• an averaged P-wave is not detectable because of the dissociation between the atrial and the ventricular depolarizations
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muscle
• 8-week old mice have a clear decrease in ZO-1 localized to the intercalated disc
• intercalated discs are punctuated by areas where there is an increase in the space between cardiac myocytes, usually near the adherens junctions
• disorganization of the electron-dense structures associated with the intercalated disc is observed
• disorganization of the myofilaments that attach to the intercalated disc also occurs
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• there is a progressive decrease in fractional shortening at 21 and 25 weeks of age
• fractional shortening degrades from a normal level at 17 weeks of age to half that of wild-type by 25 weeks of age
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