X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IN THE DOG

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。x连锁严重联合免疫缺陷是一种致命的疾病，受感染的儿童在生命早期就死于感染。我们之前在巴吉特猎犬身上发现了这种疾病的犬类模型，并开发了一个群体，结果表明，犬类疾病的临床、病理、免疫和遗传（x连锁）特征与人类的基本相同。该菌落随后被转移给Peter Felsburg博士，在伊利诺伊大学和普渡大学进行进一步的免疫学研究。1992年，Felsburg博士回到宾夕法尼亚大学，加入转诊中心，研究这种疾病的分子缺陷。虽然这个群体主要由费尔斯伯格博士的拨款支持，但转诊中心的拨款提供了一些技术援助，并支持研究犬类模型的分子遗传学。1994年，转诊中心的Henthorn博士克隆了巴吉特犬的XSCID基因，表明它与报道的人类XSCID缺陷基因相同。该基因编码几种白细胞介素共有的γ亚基，在免疫系统T细胞的增殖和功能中起重要作用。随后，转诊中心分子遗传学实验室的Henthorn博士在卡迪根威尔士柯基犬家族中发现了XSCID，其常见γ链5'编码序列中有1个碱基对缺失。威尔士柯基XSCID的一个小繁殖地，由携带雌性和骨髓移植的XSCID雄性组成，目前由Felsburg博士的NIH资助之一维持。目前资助这些菌落的目的是：(1)开发和评估改善XSCID造血干细胞移植的策略；(2)制定和评估基因治疗XSCID的策略，并评估基因治疗的潜在长期副作用；(3)评估共同γ链在非淋巴起源组织中的作用。

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.