Lipofuscin Accumulation and Gene Expression in Different Tissues of mnd Mice

• Published in: Molecular neurobiology 2012-04, Vol.45 (2), p.247-257
• Main Authors: Traina, Giovanna, Bigini, Paolo, Federighi, Giuseppe, Sitia, Leopoldo, Paroni, Gabriela, Fiordaliso, Fabio, Salio, Monica, Bendotti, Caterina, Brunelli, Marcello
• Format: Article
• Language: English
• Subjects: Adenosine triphosphatase; Animal models; Animals; ATP synthase; Biomedical and Life Sciences; Biomedicine; Blindness; Cell Biology; Central Nervous System - metabolism; Central Nervous System - pathology; Disease Models, Animal; Female; Gene expression; Gene Expression Regulation - physiology; Humans; Hydrophobicity; Lipofuscin - biosynthesis; Lipofuscin - genetics; Lipofuscin - metabolism; lysosomal storage diseases; Male; Membrane proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mitochondria; Mutation; Nervous system; Neurobiology; Neurodegeneration; Neurological complications; Neurological disorders; Neurology; Neuronal ceroid lipofuscinosis; Neuronal Ceroid-Lipofuscinoses - genetics; Neuronal Ceroid-Lipofuscinoses - metabolism; Neurons; Neurosciences; Recycling; Tissue Distribution - genetics; Tissue Distribution - physiology
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-012-8248-y

Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by neurological impairment and blindness. NCLs are almost always due to single mutations in different genes (CLN1–CLN8). Ubiquitous accumulation of undigested material and of a hydrophobic inner mitochondrial membrane protein, the subunit c of mitochondrial ATP synthase, has been described. Although protein mutation(s) in the endoplasmic reticulum–lysosomes axis can modify the trafficking and the recycling of different molecules, one of the upstream targets in these diseases may be represented by the balance of gene expression. To understand if and how neurons modify the levels of important genes during the first phases of the disease, it is important to characterize the mechanisms of neurodegeneration. Due to the impossibility of performing this analysis in humans, alternative models of investigation are required. In this study, a mouse model of human NCL8, the mnd mouse has been employed. The mnd mice recapitulate many clinical and histopathological features described in NCL8 patients. In this study, we found an altered expression of different genes in both central and peripheral organs associated with lipopigment accumulation. This is a preliminary approach, which could also be of interest in providing new diagnostic tools for NCLs.