First generation mouse models of mtDNA disease: Testing genotype/phenotype predictions

Funded Activity Summary

Mitochondrial diseases comprise a diverse group of inherited diseases affecting infants, children and adults. These disorders result from defective energy production by the mitochondria, tiny structures in all cells which have their own unique DNA. This mitochondrial DNA is inherited only from our mothers. To make energy for cells to function normally, special enzymes are produced in the mitochondria from mitochondrial and nuclear genes. In their most severe form mitochondrial disease results in infants with muti-system failure. Adult forms are less severe, with symptoms including epilepsy, cardiomyopathy, late-onset blindness or deafness, and commonly diabetes. We do not understand why different mitochondrial mutations result in such diverse symptoms, and no therapies have been consistently successful. Unusual features of mitochondrial DNA has meant that it has remained beyond the reach of techniques which are commonly used now to produce mice with altered genes. These so-called 'mouse models' are powerful tools to better understand human diseases and importantly, to enable experimental therapies to be tested and improved. This grant proposes a novel method of producing such mouse models, for the first time allowing mice with different levels of defective mitochondrial function to be produced to model the human diseases. In the proposed work, mitochondria from different mouse species will be introduced into laboratory mice. This unusual approach is based on previous work by the investigators who have shown that this produces defective mitochondria in cultured mouse cells. These mice will be allowed to age and the function of mitochondria from different organs tested as the animals age. Secondly, a range of mitochondrial DNA mutations will be produced in cultured cells and mutants selected to make other mice which should accurately model the diverse human diseases.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $256,527.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Genetics Not Elsewhere Classified

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Mitochondrial diseases: infant, child and adult | Mitochondrial genetics | Mouse disease models | Neurodegenerative and age-related diseases | Oxidative phosphorylation | late-onset opthalmic and endocrine disease | mutagenesis | somatic cell genetics

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