PUBLICATION
A Zebrafish Model of Human Barth Syndrome Reveals the Essential Role of Tafazzin in Cardiac Development and Function
- Authors
- Khuchua, Z., Yue, Z., Batts, L., and Strauss, A.W.
- ID
- ZDB-PUB-060703-2
- Date
- 2006
- Source
- Circulation research 99(2): 201-208 (Journal)
- Registered Authors
- Keywords
- cardiac development, cardiomyopathy, membrane lipids, Barth syndrome, tafazzin, zebrafish
- MeSH Terms
-
- Animals
- Cardiomyopathy, Dilated/congenital*
- Cardiomyopathy, Dilated/etiology*
- Cardiomyopathy, Dilated/genetics
- Child Development
- Disease Models, Animal
- Gene Expression Regulation, Developmental
- Heart/growth & development*
- Heart/physiology
- Humans
- Infant
- RNA, Antisense/pharmacology
- RNA, Messenger/antagonists & inhibitors
- Syndrome
- Transcription Factors/deficiency*
- Transcription Factors/genetics
- Transcription Factors/physiology
- Zebrafish
- Zebrafish Proteins/deficiency*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- PubMed
- 16794186 Full text @ Circ. Res.
Citation
Khuchua, Z., Yue, Z., Batts, L., and Strauss, A.W. (2006) A Zebrafish Model of Human Barth Syndrome Reveals the Essential Role of Tafazzin in Cardiac Development and Function. Circulation research. 99(2):201-208.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping