Different early ER-stress responses in the CLN8(mnd) mouse model of neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by epilepsy, progressive motor and cognitive decline, blindness, and by the accumulation of autofluorescent lipopigment. Late-infantile onset forms (LINCL) include those linked to mutations in CLN8 gene, encoding a transmembrane protein at the endoplasmic reticulum (ER). In the motor neuron degeneration (mnd) mouse model of the CLN8-LINCL (CLN8(mnd)), we carried out an analysis of ER stress-related molecules in CNS structures that exhibit a variable rate of disease progression (early retinal degeneration and delayed brain and motoneuron dysfunction).

Retinal oxidation, apoptosis and age- and sex-differences in the mnd mutant mouse, a model of neuronal ceroid lipofuscinosis.

Retinal degeneration is an early and progressive event in many forms of neuronal ceroid lipofuscinoses (NCLs), a heterogeneous group of neurodegenerative disorders with unknown pathogenesis. We here used the mutant motor neuron degeneration (mnd) mouse, a late-infantile NCL variant, to investigate the retinal oxidative state and apoptotic cell death as a function of age and sex. Total superoxide dismutase (SOD) activities and thiobarbituric acid-reactive substance (TBARS) levels revealed progressive increases in retinal oxyradicals and lipid peroxides of mnd mice of both sexes.