Pericytes are mural cells of brain capillaries that degenerate in multiple neurological disorders. Pericytes regulate neurovascular functions, but their role in the adult brain and disease is still poorly understood because of the lack of adequate pericyte-specific experimental models. All current pericyte-deficient models are not pericyte specific, and carry an inherited embryonic trait. Here, the Inventors generated an inducible pericyte-specific Cre line using a double-promoter strategy. The Inventors ablated adult mouse pericytes expressing Cre-dependent diphtheria toxin receptor after toxin administration. Pericyte ablation led to a rapid dysregulation of cerebral blood flow and blood-brain barrier breakdown. This was followed by behavioral deficits and neurodegenerative changes. These findings show that circulatory deficits leading to secondary neurodegeneration develop immediately after pericyte loss.
Generation of an inducible pericyte-specific CRE mouse model