Cardiac parameters in <i>w¹¹¹⁸, Oregon-R</i>, and the cardiac-specific, inducible driver line.

<p>OCT measurements of end diastolic dimension (EDD) in microns, end systolic dimension (ESD) in microns, and fractional shortening (FS) in percentage are expressed as the mean +/− SE. The values for <i>w¹¹¹⁸</i> (n = 11), <i>Oregon-R</i> (n = 12), the homozygous Gal80^ts; tincΔ4-Gal4 driver line (n = 11) were obtained from flies maintained at 26°C. The values for the Gal80^ts; tincΔ4-Gal4 driver line harboring either wt-human-SGCD (n = 16) or S151A-human-SGCD (n = 16) were obtained from flies maintained at 18°C.</p

Expression of human mutant S151A-SGCD causes an inducible and reversible dilated cardiomyopathy in adult <i>Drosophila</i>.

<p>(A) Temperature shift from 18°C to 26°C causes the induction of S151A-SGCD expression and subsequent deterioration in cardiac function. At 96 hours post induction, flies expressing S151A-SGCD demonstrate an enlargement in EDD and ESD with a resultant impairment in FS. At 96 hours, a temperature shift back to 18°C results in a repression of S151A-SGCD expression and subsequent improvement in cardiac function with return of EDD, ESD and FS to near baseline. A similar level of wt-SGCD expression after temperature shift from 18°C to 26°C does not result in deterioration in cardiac function. Each graph represents the summary data for serial OCT measurements of EDD, ESD and FS and are expressed as the mean +/− SE (n = 16 for wt-SGCD and n = 16 for S151A-SGCD). * P<0.05 for time point measurements compared to baseline and <i>#</i> P<0.05 for measurements between wt-SGCD and S151A-SGCD at each time point. (B) Representative serial OCT m-modes in individual flies expressing S151A-SGCD or wt-SGCD at the indicated times and temperatures. The arrows indicate EDD when the fly heart is fully relaxed and ESD when the fly heart if fully contracted. A 125 micron standard and 1 second scale bar is shown.</p

Expression of S151A-SGCD precedes cardiac function changes in adult <i>Drosophila</i> expressing S151A-SGCD.

<p>(A).Temperature shift from 18°C to 26°C results in deterioration in cardiac function and induction of S151A-SGCD expression. After a temperature shift to 26°C, the induction of transgene expression precedes the development of dilated cardiomyopathy by 48 hours as demonstrated by QRT-PCR measurements of S151A-SGCD mRNA levels compared to cardiac function by serial OCT. A second temperature shift back to 18°C represses S151A-SGCD mRNA expression and results in restoration of cardiac function by 48 hours. We performed three independent experiments using different batches of flies each time. The summary data for QRT-PCR at the indicated times and temperatures are expressed as the mean +/− SE of three independent experiments, each performed in triplicate. * p<0.05 for S151A-SGCD expression at indicted time vs. baseline; # p<0.05 for wt-SGCD expression at the indicated time points vs. baseline; Δ p<0.05 for wt-SGCD vs. S151A-SGCD at the 48 hour time point. (B–D) Summary data for the time course of S151A-SGCD expression (closed circles) vs. cardiac measurements (closed squares) based on serial measurements of EDD, ESD, and FS as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007132#pone-0007132-g001" target="_blank">Figure 1</a>.</p