Kir4.1 is a glial specific inwardly rectifying potassium channel. Highest expression is observed in astrocytes. Kir4.1 demonstrates robust developmental upregulation. Although Kir4.1 is expressed in all astrocytes studied, expression levels vary over 10-fold across different brain structures in adult rodents. Kir4.1 is implicated in several critical astrocytic homeostatic functions (right). Loss of Kir4.1 protein expression leads to aberrant CNS development in humans and rodents. A focus of the Olsen lab is to understand what regulates patterns of Kir4.1 gene and protein expression in typical development, so that we can better understand how loss of this protein (seen in the context of disease) contributes to aberrant CNS functioning.
Rett Syndrome is a devastating X-linked neurodevelopmental disorder affecting 1:10,000 live female births. Girls develop seemingly normal until about 12-18 months of age when they begin to demonstrate developmental regression. Hallmarks of Rett syndrome include loss of gross motor skills, breathing abnormalities, cognitive deficits, hand stereotopies, gastrointestinal dysmotility, difficulty with ambulation and seizures. Over 95% of Rett syndrome cases are caused by spontaneous mutations in the transcriptional regulator methyl binding protein 2 (MECP2). In the CNS, MeCP2 is highly expressed in neurons, but is also expressed at lower levels in astrocytes, microglia and oligodendrocytes. A focus of the Olsen lab is to better understand astrocyte function in MeCP2 deficient astrocytes and how this contributes to overall disease onset and progression.