A Critical Appraisal of the Tafazzin Knockdown Mouse Model of Barth Syndrome: What Have We Learned About Pathogenesis and Potential Treatments?

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "A Critical Appraisal of the Tafazzin Knockdown Mouse Model of Barth Syndrome: What Have We Learned About Pathogenesis and Potential Treatments?"

Pediatric heart failure remains poorly understood, distinct in many aspects from adult heart failure. Limited data point to roles of altered mitochondrial functioning and in particular, changes in mitochondrial lipids, especially cardiolipin. Barth syndrome is a mitochondrial disorder caused by tafazzin mutations that lead to abnormal cardiolipin profiles. Patients are afflicted by cardiomyopathy, skeletal myopathy, neutropenia, and growth delay. A mouse model of Barth syndrome was developed a decade ago, which relies on a doxycycline-inducible shRNA to knock down expression of tafazzin mRNA ("TAZKD"). Our objective was to review published data from the TAZKD mouse to determine its contributions to our pathogenetic understanding of, and potential treatment strategies for, Barth syndrome. In regard to the clinical syndrome, the reported physiological, biochemical, and ultrastructural abnormalities of the mouse model mirror those in Barth patients. Using this model, the PPAR pan-agonist bezafibrate has been suggested as potential therapy because it ameliorated the cardiomyopathy in TAZKD mice, while increasing mitochondrial biogenesis. A clinical trial is now underway to test bezafibrate in Barth syndrome patients. Thus, the TAZKD mouse model of Barth syndrome has led to important insights into disease pathogenesis and therapeutic targets, which can potentially translate to pediatric heart failure.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Heart and circulatory physiology
ISSN: 1522-1539


DeepDyve research library

PubMed Articles [22405 Associated PubMed Articles listed on BioPortfolio]

SERCA2a tyrosine nitration coincides with impairments in maximal SERCA activity in left ventricles from tafazzin-deficient mice.

The sarco/endoplasmic reticulum Ca -ATPase (SERCA) is imperative for normal cardiac function regulating both muscle relaxation and contractility. SERCA2a is the predominant isoform in cardiac muscles ...

Multifaceted Approach to Enhance Pill-Swallowing Ability in Children and Adults With Barth Syndrome.

People with Barth syndrome (BTHS) present with sensory and motor deficits that affect their ability to swallow medications in solid form. Inability to swallow pills can reduce opportunities for people...

Long-term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Choline is critical for normative function of 3 major pathways in the brain, including acetylcholine biosynthesis, being a key mediator of epigenetic regulation, and serving as the primary substrate f...

A conditional mouse model of complex II deficiency manifesting as Leigh-like syndrome.

Leigh syndrome embodies degenerative disorders with a collection of symptoms secondary to inborn errors of metabolism. Combinations of hypomorphic and loss-of-function alleles in many genes have been ...

First behavioural assessment of a novel Immp2l knockdown mouse model with relevance for Gilles de la Tourette syndrome and Autism spectrum disorder.

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder, which shares some clinical features with Autism spectrum disorder (ASD). The genetic factors relevant to the development of both ...

Clinical Trials [8530 Associated Clinical Trials listed on BioPortfolio]

About the Efficacy of a Serious Game in Critical Appraisal

Background: serious games have been reported as valuable method of learning since a decade. Even if their evident efficiency hasn't been always reported, their influence on the learners' m...

Taking Action: a Care for Type 2 Diabetes Intervention for Couples

Communal coping consists of the appraisal of a problem as shared and collaboration to manage the problem. Among individuals with type 2 diabetes, self-report, daily diary, and observationa...

Role of Chemokine and Chemokine Receptor in Psoriasis

This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that ...

Subcutaneous Immunotherapy for Mouse in Adults

This is an open label trial of mouse allergenic extract administered by subcutaneous injection in adults with asthma and mouse sensitivity. The study is designed to evaluate: - the saf...

Study of Immune Responses and Safety of Recombinant Human CD40 Ligand in Patients With X-Linked Hyper-IgM Syndrome

The primary goal of this Phase I/II study is to assess the immune response and safety of recombinant human CD40 ligand (rhuCD40L) in patients with X-linked hyper IgM syndrome (XHIM). XHIM...

Medical and Biotech [MESH] Definitions

Rare congenital X-linked disorder of lipid metabolism. Barth syndrome is transmitted in an X-linked recessive pattern. The syndrome is characterized by muscular weakness, growth retardation, DILATED CARDIOMYOPATHY, variable NEUTROPENIA, 3-methylglutaconic aciduria (type II) and decreases in mitochondrial CARDIOLIPIN level. Other biochemical and morphological mitochondrial abnormalities also exist.

A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.

One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.

A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.

An inbred strain of mouse that is widely used as a model for AUTOIMMUNE DISEASES such as SYSTEMIC LUPUS ERYTHEMATOSUS.

Quick Search

DeepDyve research library

Relevant Topic

Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Searches Linking to this Article