A NEW ANIMAL MODEL OF SCID FOR BIOMEDICAL RESEARCH

描述（由申请人提供）：研究人员最近描述了杰克罗素梗中SCID的发生率。 这些动物的分子缺陷是错误的可变多样性和连接重组，这是由编码DNA依赖性蛋白激酶（DNA-PKcs）的催化亚基的基因内的点突变产生的，从而产生提前终止密码子。 因此，这些犬中的SCID与先前描述的C.B-17小鼠和阿拉伯马驹中的常染色体隐性形式的SCID类似。 这项资源相关项目资助（RRPG）的目的是确保资金，以便开发这种具有潜在价值的SCID动物模型，供科学界使用。 为此，将通过骨髓移植建立纯合SCID杰克罗素梗的繁殖群体。 尽管可以设想这些动物的许多潜在用途，但有几个是显而易见的，并将被描述为开发这种新的SCID动物模型的理由。 本申请的具体目的如下：1）SCID狗作为在患有联合免疫缺陷的儿童中开发更有效的骨髓移植技术的工具; 2）SCID狗作为有缺陷的非同源DNA末端连接的模型;和3）SCID狗作为SCID小鼠的替代/补充。

DESCRIPTION (provided by applicant): The investigators recently described the incidence of a SCID in Jack Russell terriers. The molecular defect in these animals is faulty variable diversity and joining recombination, which results from a point mutation within the gene encoding the catalytic subunit of the DNA dependent protein kinase (DNA-PKcs) generating a premature stop codon. Thus, SCID in these dogs is analogous to previously described autosomal recessive forms of SCID in C.B-17 mice and in Arabian foals. The purpose of this Resource Related Project Grant (RRPG) is to secure funding so that this potentially valuable animal model of SCID can be developed for use by the scientific community. To that end, a breeding colony of homozygous SCID Jack Russell terriers will be established via bone marrow engraftment. Though many potential uses for these animals can be envisioned, several are obvious and will be delineated as justification for developing this new animal model of SCID. The Specific Aims of this application are as follows: 1) SCID dogs as a tool to develop more efficient bone marrow transplantation techniques in children afflicted with combined immunodeficiency; 2) SCID dogs as a model of defective non-homologous DNA end joining; and 3) SCID dogs as an alternative/addition to use of SCID mice.