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Journal of Neuroscience, Vol 16, 640-648, Copyright © 1996 by Society for Neuroscience
Selective failure of brain-derived neurotrophic factor mRNA expression in the cerebellum of stargazer, a mutant mouse with ataxia
X Qiao, F Hefti, B Knusel and JL Noebels
Andrus Gerontology Center, University of Southern California, Los Angeles 90089, USA.
In search of the possible involvement of neurotrophic factors in inherited
neurological disease, we examined brain-derived neurotrophic factor (BDNF),
nerve growth factor (NGF), and neurotrophin-3 (NT-3) mRNA expression
patterns in the ataxic mutant mouse stargazer (stg). Using in situ
hybridization, we found a selective and near total reduction in BDNF mRNA
in the cerebellar granule cell layer. NT-3 or NGF mRNA expression in the
cerebellum was normal. Northern blot analysis demonstrated a 70% reduction
in BDNF mRNA in the whole cerebellum. BDNF mRNA levels in other mutant
brain regions were unchanged. Absence of BDNF mRNA in granule cells was
observed at postnatal age (P15), coincident with the onset of ataxia, and
expression levels failed to follow the developmental increase found in the
wild type at later ages (P20 and P30). Despite the severe BDNF reduction,
in situ hybridization patterns for both the full-length and the truncated
BDNF TrkB receptor mRNA were unaltered. No major cytoarchitectural
abnormalities were apparent in the stg/stg cerebellum. BDNF expression in a
related ataxic mutant, tottering, was unaltered. These data show that BDNF
can be regulated selectively in distinct brain regions, possibly by
differential activation of its multiple promoters. Absence of cerebellar
granule cell BDNF mRNA in stg/stg mice demonstrates that sustained
expression of this neurotrophin is not required for cell survival in the
developing cerebellar cortex. Our data, in contrast, suggest a role of BDNF
in maturation of specific cerebellar neurons and pathways. Early failure of
cerebellar BDNF expression may be related to the ataxic phenotype in stg
mice.
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