Linked Life Data

10446925

Source:http://linkedlifedata.com/resource/pubmed/id/10446925

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-10-28
pubmed:abstractText
Effects of ex vivo GDNF gene delivery on the degeneration of motoneurons were studied in the G1H transgenic mouse model of familial ALS carrying a human superoxide dismutase (SOD1) with a Gly93Ala mutation (Gurney et al., 1994). Retroviral vectors were made to produce human GDNF or E. coli beta-galactosidase (beta-Gal) by transient transfection of the Phoenix cell line and used to infect primary mouse myoblasts. In 6-week-old G1H mice, 50,000 myoblasts per muscle were injected bilaterally into two hindlimb muscles. Untreated G1H and wild-type mice served as additional controls. At 17 weeks of age, 1 week before sacrifice, these muscles were injected with fluorogold (FG) to retrogradely label spinal motoneurons that maintained axonal projections to the muscles. There were significantly more large FG-labeled alpha motoneurons at 18 weeks in GDNF-treated G1H mice than in untreated and beta-Gal-treated G1H mice. A morphometric study of motoneuron size distribution showed that GDNF shifted the size distribution of motoneurons toward larger cells compared with control G1H mice, although the average size and number of large motoneurons in GDNF-treated mice were less than that in wild-type mice. GDNF also prolonged the onset of disease, delayed the deterioration of performance in tests of motor behavior, and slowed muscle atrophy. Quantitative, real-time RT-PCR and PCR showed persistence of transgene mRNA and DNA in muscle for up to 12 weeks postgrafting. These observations demonstrate that ex vivo GDNF gene therapy in a mouse model of FALS promotes the survival of functional motoneurons, suggesting that a similar approach might delay the progression of neurodegeneration in ALS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1853-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10446925-Amyotrophic Lateral Sclerosis, pubmed-meshheading:10446925-Animals, pubmed-meshheading:10446925-Cell Transplantation, pubmed-meshheading:10446925-Disease Models, Animal, pubmed-meshheading:10446925-Disease Progression, pubmed-meshheading:10446925-Gene Therapy, pubmed-meshheading:10446925-Genetic Vectors, pubmed-meshheading:10446925-Glial Cell Line-Derived Neurotrophic Factor, pubmed-meshheading:10446925-Humans, pubmed-meshheading:10446925-Mice, pubmed-meshheading:10446925-Motor Neurons, pubmed-meshheading:10446925-Muscle, Skeletal, pubmed-meshheading:10446925-Nerve Growth Factors, pubmed-meshheading:10446925-Nerve Tissue Proteins, pubmed-meshheading:10446925-Retroviridae, pubmed-meshheading:10446925-Transduction, Genetic, pubmed-meshheading:10446925-beta-Galactosidase
pubmed:year
1999
pubmed:articleTitle
Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis.
pubmed:affiliation
Department of Pediatrics, Children's Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL 60614, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't