Characterization of Functional Abnormalities in Hearts of Transgenic Mice Expressing Forms of Actin Capping Protein Defective in Attaching Actin Filaments to Z‐lines

Abstract

In striated muscle, the barbed ends of actin filaments are attached to Z lines. Biochemical and cell biological studies suggest that actin capping protein (CP) mediates this attachment by binding the barbed ends of actin filaments and alpha-actinin crosslinks overlapping filaments from adjacent sarcomeres. Previous transgenic studies revealed that defective interaction between CP and actin filaments causes major structural defects in sarcomere organization, leading to cardiac hypertrophy and lethality. To determine the basis of the myofibril defect, we have examined the hearts of transgenic mice using histological and immunofluorescence microscopy. The hearts of transgenic mice were hypertrophied relative to body size, with an enlargement of the ventricle wall. Immunofluorescence studies revealed an altered actin organization with disruption of myofibril architecture. To understand how this defect affects cardiac function, blood pressure was measured using an indirect tail pressure assay and ECG measurements determined. The transgenic mice had a lower systolic pressure and an increased heart rate compared to wildtype mice. In ECG studies, a significant increase for both the PR and R wave height was detected, indicative of atrial and ventricular hypertrophy, validating histological studies. This research was funded by a Faculty Development Grant, Minnesota State University-Mankato, MN.