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.

该主题项目是利用NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。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。列出的机构是针对该中心的，这不是调查人员的机构。球形细胞白细胞营养不良（GLD）或Krabbe病是一种常染色体遗传遗传遗传的神经系统疾病，这是由编码溶酶体酶半乳糖蛋白酶（GALC）的基因突变引起的。 GALC负责降解特定的半乳糖脂，其中几种对紧凑，稳定的髓磷脂的产生很重要。未能充分降解半乳糖基酰胺和心理素（半乳糖基肾上腺素）会导致人类和受GLD影响的动物在组织中观察到的特征性病理发现。这些半乳磷脂通常在活性髓鞘化过程中合成，并且在具有非常低的GALC活性的个体中，Psychosine积累。 Psychosine对形成髓磷脂形成的少突胶质细胞具有剧毒，导致其死亡和骨髓骨髓的稀少。虽然大多数人类患者在六个月大之前出现症状，并且在18个月大之前死亡，但还可以诊断出年龄较大的儿童和成人。目前唯一可用的治疗方法是异源骨髓移植（BMT）。该疾病具有三种天然发生的动物模型，即Twitcher小鼠，Cairn和West Highland White Terriers以及恒河猴。杰斐逊大学医学院的大卫·温格（David Wenger）实验室在戴维·温格（David Wenger）的实验室中克隆并进行了特征。 1996年，据报道，凯恩（Cairn）和西高地（West Highland White Terriers）在凯恩（Cairn）和西高地（West Highland White Terriers）中的基因克隆。转介中心通过与育种者合作建立了育种载体犬的菌落，并维持了RR02512。但是，该殖民地随后被转移给温格博士的赠款，并通过温格博士对这种疾病的长期NIH赠款的分包合同维持了兽医学院的动物护理设施。转诊中心人员提供了对育种，诊断测试和小儿护理的一些支持。