GLYCOGENOSIS TYPE IV IN NORWEGIAN FOREST CATS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。IV型糖原沉积症是一种常染色体隐性遗传性糖代谢错误，其特征是分支酶缺乏，导致糖原储存结构异常。与人类疾病类似的猫科动物的特征是进行性神经肌肉疾病。建立了一个繁育群体，并发表了对这种独特动物模型的自然历史和病理学的研究。这将是人类疾病治疗研究的重要模型，这种疾病就像猫的同源基因一样，会导致性成熟之前死亡。Fyfe博士已经报道了猫GSDIV正常糖原分支酶基因的克隆和突变的定义。这个殖民地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。转诊中心维持着一小部分携带者。我们先前报告了异常糖原在感觉和运动神经元中的积聚，但在中枢神经系统中没有发现神经变性。对猫的GSD IV病理进行了重新评估，以评估该疾病的神经学组成部分。对一只5个月大的患病猫的脊髓进行检查，发现腹角有大量变性的运动神经元和吞神经症。伴有腹角和背角的星形细胞增多症。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，所观察到的肌肉疾病至少有神经源性萎缩的成分。此外，这些数据表明，长期改善这种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。

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.