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Animal models
- Mitochondria

Various mouse models for mitochondrial disease have been developed over the last five years. It is hoped that these models will advance our understanding of the pathophysiology and will also be useful for developing new treatments (table 3). Most of the models were produced by nuclear gene manipulation, and some bear clinical or pathological resemblances to human mitochondrial diseases. Developing a good model for human mtDNA disorders is proving difficult because it is currently not possible to transfect mammalian mitochondria with exogenous DNA. To get around this problem, Inoue and colleagues fused synaptic nerve terminals (synaptosomes) from aged mice harbouring low levels of mtDNA deletions with cybrid cells.105 They screened the cybrid clones for detectable levels of mtDNA deletions and fused one with a mouse zygote that was implanted into a foster mother. The offspring contained a mixture of wild-type mtDNA and mtDNA with a 4.7 kb deletion. These mice share some clinical features with human mtDNA deletion disorders, but they were remarkable in two respects. First, the mice developed a nephropathy (a feature not typically found in KSS), and second, the female offspring also harboured deleted mtDNA (also not typical of KSS). Thus, like many other mouse models, there is not a complete correspondence between the human and the murine phenotype. To some extent this is inevitable—human mtDNA disorders are late onset diseases, and it is difficult to mimic the effects of aging in other shorter lived mammals. Attempts to generate mice transmitting mtDNA point mutations similar to those found in humans have not yet been forthcoming.

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