Mouse mtDNA mutant model of Leber hereditary optic neuropathy.
نویسندگان
چکیده
An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.
منابع مشابه
Finger prick blood testing in Leber hereditary optic neuropathy.
Individuals from 33 unrelated Australian families with optic atrophy were screened for 10 different single base alterations in mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) using direct polymerase chain reaction amplification of blood spots collected on Guthrie cards. This method using blood spots allows easily accessible screening for LHON mtDNA mutations w...
متن کاملThe mutant human ND4 subunit of complex I induces optic neuropathy in the mouse.
PURPOSE To produce a mouse model of Leber hereditary optic neuropathy. METHODS A mutant ND4 subunit made compatible with the universal genetic code and containing an arginine-to-histidine substitution at residue 340, or a synthetic normal human ND4 gene was delivered to the mouse visual system. The expression and effects of the mutant ND4 gene on the optic nerve and cultured retinal ganglion ...
متن کاملMitochondrial replacement in an iPSC model of Leber's hereditary optic neuropathy
Cybrid technology was used to replace Leber hereditary optic neuropathy (LHON) causing mitochondrial DNA (mtDNA) mutations from patient-specific fibroblasts with wildtype mtDNA, and mutation-free induced pluripotent stem cells (iPSCs) were generated subsequently. Retinal ganglion cell (RGC) differentiation demonstrates increased cell death in LHON-RGCs and can be rescued in cybrid corrected RGCs.
متن کاملNeuromyelitis optica (Devic's syndrome): no association with the primary mitochondrial DNA mutations found in Leber hereditary optic neuropathy.
Devic's neuromyelitis optica is a rare syndrome characterised by the combination of acute or subacute optic neuritis and transverse myelitis, in some cases considered to be a variant of multiple sclerosis. Mutations of mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) have been identified in some patients with multiple sclerosis in whom optic neuritis is a promi...
متن کاملLeber hereditary optic neuropathy and oxidative stress.
R elatively little progress has been made in developing therapies for mitochondrial diseases in modern medicine as a result of the exquisite complexity of the structural proteins and pathways associated with mitochondrial functions and our incomplete understanding of pathophysiology (1). Leber hereditary optic neuropathy (LHON), in particular, provides a unique model for understanding molecular...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 109 49 شماره
صفحات -
تاریخ انتشار 2012