Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Whole genome transcriptome analysis identifies indices of fast and slow disease progression in two ALS mouse models

ABSTRACT: Microarray analysis has been applied to the study of ALS in order to investigate gene expression in whole spinal cord homogenates of SOD1 G93A mice and human ALS cases, although the massive presence of glial cells and inflammatory factors has made it difficult to define which gene expression changes were motor neuron specific. Recently, laser capture microdissection (LCM), combined with microarray analysis, has allowed the identification of motor neuron specific changes in gene expression in mouse and human ALS cases. The aim of the present study is to combine LCM and microarray analysis to compare the gene expression profiles of motor neurons from two SOD1G93A mouse strains (129Sv and C57) with different progression of the disease in order to discover the molecular mechanisms that may contribute to the distinct phenotypes and to uncover factors underlying fast and slow disease progression Motor neurons have been isolated from the spinal cord of 129SvG93A mice, C57G93A mice and non transgenic littermates at different time points and the transcription expression profile of the isolated motor neurons has been analysed

ORGANISM(S): Mus musculus

SUBMITTER: giovanni nardo

PROVIDER: E-GEOD-46298 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis.

Nardo Giovanni G Iennaco Raffaele R Fusi Nicolò N Heath Paul R PR Marino Marianna M Trolese Maria C MC Ferraiuolo Laura L Lawrence Neil N Shaw Pamela J PJ Bendotti Caterina C

Brain : a journal of neurology 20130924 Pt 11

Amyotrophic lateral sclerosis is heterogeneous with high variability in the speed of progression even in cases with a defined genetic cause such as superoxide dismutase 1 (SOD1) mutations. We reported that SOD1(G93A) mice on distinct genetic backgrounds (C57 and 129Sv) show consistent phenotypic differences in speed of disease progression and life-span that are not explained by differences in human SOD1 transgene copy number or the burden of mutant SOD1 protein within the nervous system. We aime ...[more]

PMID: 24065725

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Project description:ALS is a uniformly fatal neurodegenerative disease in which motor neurons in the spinal cord and brain stem are selectively lost. Individual motor - groups of motor neurons innervating single muscles - show widely varying degrees of disease resistance: in the final stages of ALS, nearly all voluntary movement is lost but eye movement and eliminative and sexual functions remain relatively unimpaired. These functions are controlled by motor neurons of the oculomotor (III), trochlear (IV) and abducens (VI) nuclei in the midbrain and brainstem, and by Onuf's nucleus in the lumbosacral spinal cord, respectively. Correspondingly, in ALS autopsies the oculomotor and Onuf's nuclei are almost completely preserved. We used microarray profiling of isolated wildtype mouse motor neurons to identify genes whose expression was characteristic of both oculomotor and Onuf's nuclei but not of vulnerable lumbar spinal neurons, or vice versa. Three wild-type C57BL/6J P7 male animals were perfused with 30% sucrose, lumbosacral spinal cord and midbrain regions were rapidly recovered, embedded in OCT compound, and frozen in liquid nitrogen. 12 um-thick cryosections were mounted on RNAse-free, PEN-foil covered glass slides (Zeiss), fixed for 2 min in 100% EtOH, rinsed in 50% EtOH, stained with 1% cresyl violet for 2 min, rinsed with 50% EtOH, dehydrated in graded solutions of ethanol and air dried prior to LCM using PALM Microbeam system (Zeiss). From each animal, ~200 DL, L5, and oculomotor motor neurons were collected directly in lysis buffer. RNA was purified using Absolutely RNA, NanoPrep kit (Stratagene, La Jolla, CA). RNA integrity was assessed on the Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA). At least 1.5 ng of purified RNA was the starting material used in the WT-Ovation Pico RNA Amplification System (Nugen, San Carlos,CA) with the FL-Ovation cDNA Biotin Module V2 (Nugen) to generate labeled probe. 10 ug of biotinylated cRNA from three independent samples for each motor neuron group isolated by LCM was hybridized to on Affymetrix (Santa Clara, CA) Mouse Genome 430 2.0 Arrays. Gene ontology and pathway analysis was performed using DAVID Bioinformatics Resources 6.7 (National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD).

Dataset Information

Whole genome transcriptome analysis identifies indices of fast and slow disease progression in two ALS mouse models

Publications

Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis.

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