A NEW ANIMAL MODEL OF SCID FOR BIOMEDICAL RESEARCH

描述(由申请人提供)：调查人员最近描述了杰克·罗素梗犬发生SCID的情况。这些动物的分子缺陷是错误的变量多样性和连接重组，这是由于编码DNA依赖蛋白激酶催化亚单位(DNA-PKcs)的基因内的点突变产生了过早终止密码子。因此，这些狗的SCID类似于先前在C.B-17小鼠和阿拉伯马驹中描述的常染色体隐性SCID形式。这项与资源相关的项目资助(RRPG)的目的是为了获得资金，以便开发这种潜在有价值的SCID动物模型，供科学界使用。为此，将通过骨髓移植建立一个纯合SCID杰克·罗素梗犬的繁育群体。 虽然这些动物的许多潜在用途是可以预见的，但其中一些是显而易见的，并将被描述为开发这种新的SCID动物模型的理由。 这项应用的具体目的如下：1)SCID犬作为一种工具，用于开发更有效的联合免疫缺陷儿童的骨髓移植技术；2)SCID犬作为缺陷非同源DNA末端连接的模型；以及3)SCID犬作为SCID小鼠的替代/补充使用。

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.