A NEW ANIMAL MODEL OF SCID FOR BIOMEDICAL RESEARCH

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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.