Expression and neurobehavioral analyses in prosaposin deficient mice: Molecular alterations precede neuronal deficits. Mus musculus

Prosaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases in lysosomes. To explore the molecular mechanism(s) of disease progression, temporal transcriptome microarray analyses of cerebrum and cerebellum tissues were conducted using mRNA from three prosaposin deficiency mouse models: PS-NA (hypomorphic prosaposin deficiency), PS-/- (prosaposin null) and 4L/PS-NA (a V394L/V394L glucocerebrosidase mutation and PS-NA) mice. Our results indicate that regionally specific gene expression abnormalities preceded the histological and behavioral changes and CEBPD is a candidate regulator of brain disease in prosaposin deficiency. The alterations of gene expression are detected at birth and are more profound in cerebellum than cerebrum. Keywords: disease-state analysis Overall design: In order to increase the temporal resolution of expression profile in brain, the disease progression in those models were inverstigated in two regions of brains (cerebellum and cerebrum) at three or four time points according to the genotypes. PS-/-: new born (0d), 10 days (10d), 20 days (20d), 25 days (25d); PS-NA: new born, 4 weeks (4w), 12 weeks (12w), 18 weeks (18w); 4L/PS-NA: 4 weeks (4w), 12 weeks (12w), 18 weeks (18w). The data from those models were analyzed relative to the corresponding wild type at same time point (0d, 10d, 20d, 4w, 12w, 18w).