GLYCOGENOSIS TYPE IV IN NORWEGIAN FOREST CATS

挪威森林猫的 IV 型糖原分解作用

• 批准号: 7391950
• 负责人: MARK E HASKINS
• 金额: $ 0.07万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391950
• 关键词: GLYCOGENOSIS; TYPE; IV; NORWEGIAN; FOREST

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Glycogenosis type IV is an autosomal recessive inborn error of carbohydrate metabolism in which the deficiency of branching enzymes results in storage of glycogen with an abnormal structure. The feline homolog of the human disease is characterized by progressive neuromuscular disease. A breeding colony was established and studies of the natural history and pathology of this unique animal model have been published. This will be an important model for studies of therapy of the human disease, which like the feline homolog, causes death before sexual maturity. The cloning of the normal glycogen branching enzyme gene and definition of the mutation in feline GSDIV have been reported by Dr. Fyfe. Most of this colony was transferred to Michigan State University for study by Dr. Fyfe under separate support. A small nucleus of carriers is being maintained by the Referral Center. We previously reported accumulation of abnormal glycogen in sensory and motor neurons, but neurodegeneration in the CNS was not noted. Reevaluation of the feline GSD IV pathology was undertaken to assess the neurologic component of the disorder. Examination of spinal cord of a 5 month-old affected cat revealed degenerative large (motor) neurons and neuronophagia in ventral horns. This was accompanied by astrocytosis in both ventral and dorsal horns. These data indicate that deficiency of branching enzyme activity in the feline nervous system is neuropathic and that the observed muscle disease has at least a component of neurogenic atrophy. Further, these data indicate that effort at long term amelioration of the disease will very likely have to address the tissue specific effects in the CNS.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。 IV型糖原增多症是一种常染色体隐性先天性碳水化合物代谢异常，其中分支酶的缺乏导致糖原储存结构异常。人类疾病的猫科动物同源物的特征是进行性神经肌肉疾病。建立了一个繁殖群体，并发表了关于这种独特动物模型的自然历史和病理学的研究。这将成为人类疾病治疗研究的重要模型，这种疾病与猫科动物的同源疾病一样，会导致性成熟前死亡。 Fyfe 博士报道了猫 GSDIV 正常糖原分支酶基因的克隆和突变的定义。该群体的大部分被转移到密歇根州立大学，由法伊夫博士在单独的支持下进行研究。转诊中心正在维护一小部分携带者核心。我们之前报道过感觉和运动神经元中异常糖原的积累，但没有注意到中枢神经系统中的神经变性。对猫 GSD IV 病理学进行重新评估，以评估该疾病的神经系统成分。对 5 个月大受影响猫的脊髓检查显示，大（运动）神经元退化，腹角出现神经吞噬现象。这伴随着腹角和背角的星形细胞增多。这些数据表明，猫神经系统中分支酶活性的缺乏是神经性的，并且观察到的肌肉疾病至少具有神经源性萎缩的一个组成部分。此外，这些数据表明，长期改善该疾病的努力很可能必须解决中枢神经系统中的组织特异性影响。