PMID- 8551348 OWN - NLM STAT- MEDLINE DCOM- 19960222 LR - 20191101 IS - 0270-6474 (Print) IS - 1529-2401 (Electronic) IS - 0270-6474 (Linking) VI - 16 IP - 2 DP - 1996 Jan 15 TI - Selective failure of brain-derived neurotrophic factor mRNA expression in the cerebellum of stargazer, a mutant mouse with ataxia. PG - 640-8 AB - 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. FAU - Qiao, X AU - Qiao X AD - Andrus Gerontology Center, University of Southern California, Los Angeles 90089, USA. FAU - Hefti, F AU - Hefti F FAU - Knusel, B AU - Knusel B FAU - Noebels, J L AU - Noebels JL LA - eng GR - AG09793/AG/NIA NIH HHS/United States GR - AG10480/AG/NIA NIH HHS/United States GR - NS22933/NS/NINDS NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Ataxia/*genetics MH - Autoradiography MH - Brain-Derived Neurotrophic Factor MH - Cerebellum/*physiology MH - Gene Expression/*genetics MH - Mice MH - Mice, Mutant Strains MH - Nerve Tissue Proteins/*genetics MH - Phenotype MH - RNA, Messenger/*genetics PMC - PMC6578657 EDAT- 1996/01/15 00:00 MHDA- 1996/01/15 00:01 PMCR- 1996/07/15 CRDT- 1996/01/15 00:00 PHST- 1996/01/15 00:00 [pubmed] PHST- 1996/01/15 00:01 [medline] PHST- 1996/01/15 00:00 [entrez] PHST- 1996/07/15 00:00 [pmc-release] AID - 10.1523/JNEUROSCI.16-02-00640.1996 [doi] PST - ppublish SO - J Neurosci. 1996 Jan 15;16(2):640-8. doi: 10.1523/JNEUROSCI.16-02-00640.1996.