Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal development.
Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative disorder with abnormal lipid storage as the major cellular pathologic hallmark. Genetic analyses have identified mutations in NPC1 gene in the great majority of cases, while mutations in NPC2 account for the remainders. Yet little is known regarding the cellular mechanisms responsible for NPC pathogenesis, especially for neurodegeneration, which is the usual cause of death. To identify critical steps that could account for the pathological manifestations of the disease in one of the most affected brain structures, we performed global gene expression analysis in the cerebellum from 3-week old Npc1+/+ and Npc1-/- mice with two different microarray platforms (Agilent and Illumina). Differentially expressed genes identified by both microarray platforms were then subjected to KEGG pathway analysis. Expression of genes in six pathways was significantly altered in Npc1-/- mice; functionally, these signaling pathways belong to the following three categories: (1) steroid and terpenoid biosynthesis, (2) immune response, and (3) cell adhesion/motility. In addition, the expression of several proteins involved in lipid transport was significantly altered in Npc1-/- mice. Our results provide novel molecular insight regarding the mechanisms of pathogenesis in NPC disease and reveal potential new therapeutic targets.
Department of Basic Medical Sciences, COMP, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Guanghong
G
Liao
Zhining
Z
Wen
Kristopher
K
Irizarry
Ying
Y
Huang
Katherine
K
Mitsouras
Mariam
M
Darmani
Terry
T
Leon
Leming
L
Shi
Xiaoning
X
Bi
D000818:Animals; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins