GALACTOCEREBROSIDASE DEFICIENCY IN THE DOG - MODEL OF KRABBE DISEASE IN HUMANS

狗的半乳糖脑苷酶缺乏症 - 人类克拉伯病模型

• 批准号: 7391958
• 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/7391958
• 关键词: GALACTOCEREBROSIDASE; DEFICIENCY; DOG; MODEL; KRABBE

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. Globoid cell leukodystrophy (GLD) or Krabbe disease is an autosomal recessively inherited neurological disease caused by mutations in the gene coding for the lysosomal enzyme galacto-cerebrosidase (GALC). GALC is responsible for the degradation of specific galactolipids, including several that are important in the production of compact, stable myelin. A failure to adequately degrade galactosylceramide and psychosine (galactosylsphingosine) results in the characteristic pathological findings observed in tissue from humans and animals affected with GLD. These galactosphingolipids are normally synthesized during active myelination, and psychosine accumulates in individuals with very low GALC activity. Psychosine is highly toxic to the myelin-forming oligodendrocytes, causing their death and the paucity of myelin found on autopsy. While most human patients present with symptoms before six months of age and die before 18 months of age, older children and adults can also be diagnosed with GLD. The only treatment available at this time is heterologous bone marrow transplantation (BMT). This disease has three naturally occurring animal models, the twitcher mouse, the Cairn and West Highland White terriers, and the rhesus monkey. The human, mouse, and monkey GALC genes have been cloned and characterized in the laboratory of David Wenger, PhD, at the Jefferson University School of Medicine. Cloning of the gene in Cairn and West Highland White Terriers was reported in 1996. The colony of breeding carrier dogs was established by the Referral Center by working with breeders and was maintained RR02512. However, the colony was subsequently transferred to Dr. Wenger¿s grant and have been maintained within the Veterinary School¿s animal care facilities by a subcontract from Dr. Wenger¿s long-standing NIH grant on this disorder. Some support for breeding, diagnostic testing, and pediatric care is provided by the Referral Center personnel.

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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。球样细胞脑白质营养不良（GLD）或克拉伯病是一种常染色体隐性遗传性神经系统疾病，由编码溶酶体酶半乳糖苷酶（GALC）的基因突变引起。GALC负责降解特定的半乳糖脂，包括在产生致密、稳定的髓鞘中重要的几种半乳糖脂。未能充分降解半乳糖神经酰胺和精神病（半乳糖鞘氨醇）导致在患有GLD的人和动物组织中观察到特征性病理学发现。这些半乳糖鞘脂通常在活跃的髓鞘形成过程中合成，并且在具有非常低的GALC活性的个体中积累精神病肽。普索辛对形成髓鞘的少突胶质细胞有剧毒，导致它们死亡，尸检发现髓鞘缺乏。虽然大多数人类患者在6个月大之前出现症状，并在18个月大之前死亡，但年龄较大的儿童和成人也可被诊断为GLD。目前唯一可用的治疗方法是异源骨髓移植（BMT）。这种疾病有三种自然发生的动物模型，抽搐小鼠，凯恩和西部高地白色梗，和恒河猴。人类、小鼠和猴的GALC基因已经在杰斐逊大学医学院的大卫温格博士的实验室中被克隆和表征。1996年报道了凯恩梗和西部高地白色梗中该基因的克隆。由转介中心通过与育种者合作建立了育种携带犬的殖民地群体，并保持为RR 02512。然而，殖民地随后被转移到温格博士的赠款，并一直保持在兽医学校的动物护理设施内的一名医生从温格博士的长期NIH赠款对这种疾病。转介中心的工作人员提供一些育种、诊断测试和儿科护理方面的支持。