Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of spinal cords from nmd mice tranplanted with ALDHhiSSClo neural stem cells to study molecular mechanism of delayed SMARD1 disease progression induced by the transplantation.


ABSTRACT: SMARD1 is an infantile autosomal recessive motor neuron (MN) disease, caused by mutations in the Immunoglobulin mu binding protein 2 (IGHMBP2). We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) to modify disease progression of nmd mice, an animal model of SMARD1. ALDHhiSSClo stem cells are self-renewing and multipotent and when intratechally transplanted in nmd mice generate motor neurons properly localized in the spinal cord ventral horns. Transplanted nmd animals presented delayed disease progression, sparing of motor neurons and ventral root axons and increased life-span. To further investigate the molecular events responsible for these differences, microarray and Real time RT-PCR analysis of wild-type, mutated and transplanted nmd spinal cord were undertaken. We demonstrated a down-regulation of genes involved in excitatory amino acid toxicity and oxidative stress handling, as well as an up-regulation of genes related to the chromatin organization in nmd compared to wild-type mice, suggesting that they may play a role in SMARD1 pathogenesis. Spinal cord of nmd transplanted mice expressed high transcript levels for genes related to neurogenesis such as Doublecortin (DCX), LIS1 and drebrin. The presence of DCX-expressing cells in adult nmd spinal cord suggests that both exogenous and endogenous neurogenesis may contribute to the observed nmd phenotype amelioration. Experiment Overall Design: We intratechally transplanted a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) in nmd mice, an animal model of SMARD1. Experiment Overall Design: We analyzed the lumbar spinal cord tract of transplanted nmd mice (n=3), untransplanted nmd mice (n=3) and wild-type mice (n=3) (all mice are of male gender). The latter groups underwent surgical procedure with vehicle. The surgical procedure and cell transplantation were done at P1 and the animals were sacrificed at 6 weeks of age.

ORGANISM(S): Mus musculus

DISEASE(S): SMARD1

SUBMITTER: Stefania Corti 

PROVIDER: E-GEOD-3075 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transplanted ALDHhiSSClo neural stem cells generate motor neurons and delay disease progression of nmd mice, an animal model of SMARD1.

Corti Stefania S   Locatelli Federica F   Papadimitriou Dimitra D   Donadoni Chiara C   Del Bo Roberto R   Crimi Marco M   Bordoni Andreina A   Fortunato Francesco F   Strazzer Sandra S   Menozzi Giorgia G   Salani Sabrina S   Bresolin Nereo N   Comi Giacomo P GP  

Human molecular genetics 20051208 2


Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an infantile autosomal-recessive motor neuron disease caused by mutations in the immunoglobulin micro-binding protein 2. We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase (ALDH) activity to modify disease progression of nmd mice, an animal model of SMARD1. ALDH(hi)SSC(lo) stem cells are self-renewing and multipotent and when intrathecally transplanted in n  ...[more]

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