T Cell Lymphopenia in Severe Congenital Neutropenia Type 5 Mouse Model

VPS45 is a regulator of membrane trafficking. Severe Congenital Neutropenia Type 5 (SCN5) is associated with mutations in VPS45. VPS45 is ubiquitously expressed, while SCN5 is characterized by a reduction in neutrophils. The focus of this work is to discover the link between VPS45 and SCN5. In collaboration with the Newburger lab, a mouse model of the SCN5 mutation was created. Initial discoveries of the mouse model parallel the SCN5 phenotype, failure to thrive, with lower weights and a smaller appearance. It was discovered that T cell lymphopenia was the primary effect of these VPS45 KI mutations. The VPS45 mutant T cells have a more activated phenotype. The development of the VPS45 mutant T cells were abnormal, lacking some of the initial stages of development in the thymus. This work, although preliminary, illuminates the importance of VPS45 and proper membrane trafficking in immune cells.