Barth syndrome is an X-linked disorder characterized by cardiomyopathy, skeletal 
myopathy, neutropenia, organic aciduria, and growth retardation caused by 
mutations in tafazzin. The sequence similarity of tafazzin to acyltransferases 
suggests a role in mitochondrial phospholipid metabolism. To study the role of 
tafazzin in heart function and development, we created a knockdown zebrafish 
model. Zebrafish tafazzin mRNA is first evident at 7 hours post-fertilization 
(hpf). At 10 and 24 hpf, tafazzin mRNA is ubiquitous, with highest levels in the 
head. By 51 hpf, expression becomes cardiac restricted. The tafazzin knockdown 
created by antisense morpholino yolk injection resulted in dose-dependent 
lethality, severe developmental and growth retardation, marked bradycardia and 
pericardial effusions, and generalized edema, signs that resemble human Barth 
syndrome heart failure. This knockdown phenotype was rescued by concomitant 
injection of normal tafazzin mRNA. Abnormal cardiac development, with a linear, 
nonlooped heart, and hypomorphic tail and eye development proves that tafazzin 
is essential for overall zebrafish development, especially of the heart. The 
tafazzin knockdown zebrafish provides an animal model similar to Barth syndrome 
to analyze the severity of human mutants and to test potential treatments.