Lymphocyte phenotype in a mouse model of 22q11.2 deletion syndrome

Abstract

Abstract Mice modeling the hemizygous deletion of chromosome 22q11.2 (22qMc) have been utilized to address various clinical phenotypes associated with the disease, including cardiac malformations, altered neural circuitry and behavioral deficits. Yet, the status of the immune system, an important clinical concern among 22q11.2 deletion syndrome (22qDS) patients, has not yet been addressed in this model despite the well-known effects of the immune system in regulating body homeostasis. While infancy and early childhood in 22qDS are associated with deficient T cell numbers due to thymic hypoplasia, which can be severe in a small subset of patients, clinical studies suggest a normalization of the T cell counts by adulthood. For the first time, we have studied the immune system in 22qMc and find that adult 22qMc do not exhibit thymic hypoplasia, immunodeficiencies of lymphoid organs, or altered T cell activation. Furthermore, deletion of the 22q11.2 homologous region does not affect T cell differentiation. Thus, this model accurately reflects the normalization of the T cell compartment in adulthood, as has been reported in human 22qDS. Altogether, our data suggest that 22qMc may serve as novel model to address experimental and translational aspects of immunity in adult 22qDS.