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Animal and Cellular Models of Barth Syndrome

Research

At present, there are several models of Barth syndrome, each of which has its own unique characteristics. All models show a cardiolipin dysfunction. For any questions or comments, please reach out to melissa.huang@barthsyndrome.org

Research Models

Knockout Models:

1) TAFAZZIN Knockout Mouse (KO) is available via Doug Strathdee, Beatson Institute. Two articles have discussed the KO mouse, the first by Doug Strathdee et al (2015) describes the meiotic challenges in generating the model. The second by Bill Pu et al (2020) characterizes the model and and assesses the impact of AAV-TAFAZZIN gene replacement therapy in a global and cardiac-specific KO models.

2) A second TAFAZZIN FLOXED mouse model was generated by utilizing the CRISPR/ Cas9 system (Xi Fang et al, 2020). Cardiomyocyte-specific TAFAZZIN KO mice display dilated cardiomyopathy with impaired but stable fractional shortening. Mitochondrial contact sites, the cristae organizing system, and F1F0-ATP synthase complexes, required for cristae morphogenesis, were abnormal, resulting in onion-shaped mitochondria. Organization of high molecular weight respiratory chain supercomplexes was also impaired.

Knockdown model: PLEASE NOTE - breeding pairs are no longer available, and new requests will involve cryorecovery.

Knockdown mouse model (KDown) is available from Jackson Laboratories (B6.Cg-Gt(ROSA)26Sortm37(H1/tetO-RNAi:Taz)Arte/ZkhuJ. and was made using a siRNA transgene at the ROSA26 locus to lower the expression of the endogenous mouse tafazzin gene. The model is inducible using doxycycline, and it was made using the proprietary technology of TaconicArtemis, GmbH (Köln, Germany) under contract from BSF.

Kdown mouse review: A critical appraisal of the tafazzin knockdown mouse model of Barth syndrome: what have we learned about pathogenesis and potential treatments? Ren M, Miller PC, Schlame M, Phoon CKL. Am J Physiol Heart Circ Physiol. 2019 Dec 1;317(6):H1183-H1193. doi: 10.1152/ajpheart.00504.2019

Cellular models of Barth syndrome have used shRNAs in rodent cardiac cells to lower tafazzin gene expression in different primary cell lines. The publications for these models are listed below.

Drosophila models of Barth syndrome utilize the imprecise excision of a P element from stock y. Below is a list of publications.

A yeast model of Barth syndrome has also been used extensively. Below is a list of publications.

Human iPS cells and mouse embryonic fibroblasts are also represented in Barth syndrome as shown in the publications below.

A zebra fish model has also been described.

*Publications that acknowledge financial support contributed by BSF and/or BSF Affiliates.

▼Publications that acknowledge biological samples (and/or information) from Barth families, the Barth Syndrome Registry and Repository (BRR), and/or BSF Affiliates.

 

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