International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 164 - SENSITIVITY OF STRIATAL PROJECTION NEURONS TO MITOCHONDRIAL DYSFUNCTION

IN OMI DEFICIENT MND2 MICE

Jones JM 1, Tallaksen-Greene S 2, Albin RL 2, Meisler MH 1

1 University of Michigan, Department of Human Genetics, Ann Arbor, United States, 2 University of Michigan, Department of Neurology, Ann Arbor, United States

The Ser276Cys mutation in the mitochondrial protease OMI (Prss25) is responsible for neurodegeneration and muscle atrophy in the mnd2 mouse (Jones et al, Nature 2003).  Neuronal degeneration and gliosis are first detectable in the striatum, with other brain regions becoming involved later in disease progression (Rathke-Hartlieb et al, Expt. Neurol. 2002).  To identify the sensitive striatal neurons, brain sections from early stages of the disease were stained with antisera identifying striatal neuron subpopulations.  Normal numbers of  somatostatin-containing and cholinergic interneurons were detected.  A dramatic reduction in striatal projection neurons containing substance P and enkephalin was indicated by reduced staining within their target structures, the substantia nigra and globus pallidus, respectively. This is the same pattern of pathology found in Huntington's Disease (HD), consistent with prior suggestions of mitochondrial dysfunction in HD.  Ultrastructural studies of tissues from mnd2 mice reveal swollen and disorganized mitochondria in brain, cardiac muscle and skeletal muscle, confirming the biochemical evidence for mitochondrial dysfunction.  We are testing OMI as a candidate gene for human mitochondrial encephalomyopathies in which muscle and brain are both affected. 

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