X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN THE DOG

狗的 X 连锁严重联合免疫缺陷病

• 批准号: 7391952
• 负责人: Peter J Felsburg
• 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/7391952
• 关键词: LINKED; SEVERE; COMBINED; IMMUNODEFICIENCY; DOG

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. X-linked severe combined immunodeficiency is a lethal disorder in which affected children succumb early in life to infection. We had previously identified a canine model of this disorder in the Basset Hound, and developed a colony in which it was shown that the clinical, pathologic, and immunologic as well as genetic (X-linked) characteristics of the canine disease are essentially identical to those in humans. The colony was subsequently transferred to Dr. Peter Felsburg for further immunologic studies at the University of Illinois and Purdue University. Dr. Felsburg returned to the University of Pennsylvania in 1992 and joined the Referral Center, to define the molecular defect in this disorder. While the colony was supported primarily by Dr. Felsburg's grants, the Referral Center grant provided some technical assistance, as well as support for working out the molecular genetics of the canine model. In 1994, Dr. Henthorn of the Referral Center cloned the Basset XSCID gene, showing that it is the same gene as reported to be defective in human XSCID. The gene encodes the gamma subunit common to several interleukins, which play an important role in the proliferation and function of T cells of the immune system. Subsequently, Dr. Henthorn, in the Molecular Genetics Lab of the Referral Center identified XSCID in a family of Cardigan Welsh Corgis with a 1 base pair deletion in the common gamma chain 5' coding sequence. A small breeding colony of Welsh Corgi XSCID, consisting of carrier females and bone marrow transplanted XSCID males, is currently being maintained by one of Dr. Felsburg¿s NIH grants. These colonies are currently funded to: (1) Develop and evaluate strategies for improving hematopoietic stem cell transplantation for XSCID; (2) Develop and evaluate strategies for treating XSCID with gene therapy and to evaluate the potential long-term side effects of gene therapy; and (3) Evaluate the role of the common gamma chain in tissues other than of lymphoid origin.

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。X连锁严重联合免疫缺陷是一种致命的疾病，受影响的儿童在生命早期就会死于感染。我们之前已经在巴塞特猎犬身上发现了这种疾病的犬模型，并建立了一个群体，在这个群体中，这种犬病的临床、病理、免疫学和遗传(X连锁)特征基本上与人类的相同。这个群体随后被转移到彼得·费尔斯堡博士那里，在伊利诺伊大学和普渡大学进行进一步的免疫学研究。费尔斯堡博士于1992年回到宾夕法尼亚大学，并加入了转诊中心，以确定这种疾病的分子缺陷。虽然这个群体主要由费尔斯堡博士的拨款支持，但转诊中心的拨款提供了一些技术援助，并为研究犬模型的分子遗传学提供了支持。1994年，参考中心的Henthorn博士克隆了Basset XSCID基因，表明该基因与已报道的人类XSCID缺陷基因相同。该基因编码几种白介素所共有的伽马亚基，在免疫系统T细胞的增殖和功能中发挥重要作用。随后，Henthorn博士在参考中心的分子遗传学实验室中发现了一个Cardigan威尔士柯基犬家族中的XSCID，该家族在共同的伽马链5‘编码序列中存在1个碱基对缺失。一个小的威尔士柯基XSCID繁殖群体，由携带者雌性和骨髓移植的XSCID雄性组成，目前由NIH的一位费尔斯堡·S博士资助维持。这些克隆目前被资助用于：(1)开发和评估改善XSCID的造血干细胞移植的策略；(2)开发和评估用基因疗法治疗XSCID的策略，并评估基因治疗的潜在长期副作用；以及(3)评估常见的伽马链在淋巴来源以外的组织中的作用。