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资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。糖原病IV型是一种碳水化合物代谢的常染色体隐性先天误差，其中分支酶的缺乏会导致用异常结构储存糖原。人类疾病的猫同源物的特征是进行性神经肌肉疾病。建立了一个繁殖菌落，并对这种独特动物模型的自然史和病理学进行了研究。这将是研究人类疾病治疗的重要模型，就像猫同源物一样，在性成熟之前会导致死亡。 Fyfe博士报道了正常糖原分支酶基因的克隆和猫GSDIV中突变的定义。 Fyfe博士在单独的支持下将这个殖民地的大部分转移到密歇根州立大学学习。转介中心正在维持一个载体的小核。我们先前报道了感觉神经元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退行性。对猫GSD IV病理进行了重新评估，以评估该疾病的神经系统成分。检查一只5个月大的猫的脊髓检查显示腹角中的大型（运动）神经元和神经噬细胞。这伴随着腹角和背角的星形胶质细胞增多症。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成分。此外，这些数据表明，长期改善该疾病的努力很可能不得不解决中枢神经系统中组织的特定作用。