期刊
BRAIN RESEARCH
卷 1266, 期 -, 页码 18-28出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2009.02.035
关键词
Vps 33a; Hermansky-Pudlak syndrome; Purkinje cell; Cerebellum; GFAP; SHIRPA
资金
- NCI NIH HHS [CA-16056, P30 CA016056] Funding Source: Medline
- NEI NIH HHS [EY-12104, R01 EY012104] Funding Source: Medline
- NHLBI NIH HHS [HL-31698, HL-51480, R01 HL051480, R01 HL031698] Funding Source: Medline
A mutation in the Vps33a gene causes Hermansky-Pudlak Syndrome (HPS)-like-symptoms in the buff (bp mouse mutant. The encoded product, Vps33a, is a member of the Sec1 and Class C multi-protein complex that regulates vesicle trafficking to specialized lysosome-related organelles. As Sec1 signaling pathways have been implicated in pre-synaptic function, we examined brain size, cerebellar cell number and the behavioral phenotype of bf mutants. Standardized behavioral tests (SHIRPA protocols) demonstrated significant motor deficits (e.g., grip strength, righting reflex and touch escape) in bf mutants, worsening with age. Histological examination of brain revealed significant Purkinje cell loss that was confirmed with staining for calbindin, a calcium binding protein enriched in Purkinje cells. This pathologic finding was progressive, as older bf mutants (13-14 months) showed a greater attrition of neurons, with their cerebella appearing to be particularly reduced (similar to 30%) in size relative to those of age-matched-control cohorts. These studies suggest that loss of Purkinje neurons is the most obvious neurological atrophy in the bf mutant, a structural change that generates motor coordination deficits and impaired postural phenotypes. It is conceivable therefore that death of cerebellar cells may also be a clinical feature of HPS patients, a pathological event which has not been reported in the literature. in general, the bf mutant may be a potentially new and useful model for understanding Purkinje cell development and function. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据