Canine X-linked severe combined immunodeficiency. A model for investigating the requirement for the common gamma chain (gamma c) in human lymphocyte development and function.

Our laboratory has identified and characterized an X-linked severe combined immunodeficiency (XSCID) in dogs that is due to mutations in the common gamma (γc) subunit of the interleukin-2 (IL2), IL4, IL7, IL9, and IL 15 receptors. Canine XSCID, unlike genetically engineered γc-deficient mice, has a clinical and immunologic phenotype virtually identical to human XSCID. It appears that speciesspecific differences exist in the role of the γc and its associated cytokines in mice compared to their role in humans and dogs, suggesting γc-deficient dogs may be a more relevant model for studing the role of the γc in humans. We are utilizing this model for a variety of studies to address: 1. Fundamental questions concerning the role of the γc in cytokine regulation and lymphocyte development. 2. The pathogenesis of XSCID. 3. Strategies for improving bone marrow transplantation outcome. 4. Development and evaluation of strateies for gene therapy. 5. Human hematopoietic stem cell development.