Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient miceReportar como inadecuado

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BMC Neuroscience

, 9:76

First Online: 01 August 2008Received: 28 March 2008Accepted: 01 August 2008


BackgroundProsaposin encodes, in tandem, four small acidic activator proteins saposins with specificities for glycosphingolipid GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies.

ResultsOur hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null PS- and a V394L-V394L glucocerebrosidase mutation combined with PS-NA 4L-PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT-enhancer-binding protein delta CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport.

ConclusionThese results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

AbbreviationsCEBPDCCAAT-enhancer-binding protein delta

CNScentral nervous system

MBPmyelin basic protein




Calb1calbindin 28K

Pcp2Purkinje cell protein 2

Casp3caspase 3

Nfianuclei factor Ia

EMElectron Microscopy.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-9-76 contains supplementary material, which is available to authorized users.

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Autor: Ying Sun - Li Jia - Michael T Williams - Matt Zamzow - Huimin Ran - Brian Quinn - Bruce J Aronow - Charles V Vorhees -

Fuente: https://link.springer.com/

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