Abstracts

Rationale: Landau-Kleffner syndrome (LKS) is a rare childhood disorder characterized as a language disability, abnormal electroencephalogram (EEG) and often rolandic epilepsy. Onset occurs after the development of speech, in children from 4 - 7 years, with up to 80% of patients experiencing seizures and nearly all have abnormal EEG recording. LKS presents with language disorder, sleep disturbances, and possible autoimmune dysfunction Recently, SRPX2 (sushi repeat protein X-linked 2) has been identified in patients with rolandic seizures, language disability and intellectual disability. A screen for candidate molecules that interact with SRPX2 identified six molecules, including cathepsin B, ADAMTS4 (aggrecanase 1), protocadherin 10, and uPAR Previous studies with mice lacking uPAR (also known as Plaur) have shown abnormal EEG and seizures, with cognitive impairment. The Srpx2 expression is largely unknown, as is the interaction between Srpx2 and Plaur in the developing and adult brains. Methods: In situ hybridization and immunohistochemistry were used to reveal the expression patterns of Plaur and Srpx2 during embryonic and postnatal development. Biochemical analysis examined the changes in Srpx2 expression in the absence of Plaur. Results: Sprx2 is selectively expressed in neuronal progenitors and neurons in the developing forebrain. The embryonic patterns of Plaur and Srpx2 are overlapping within the emerging cerebral wall. The expression patterns of Srpx2 in the adult mouse correspond to a role in sleep regulation, motor control, and attention. Finally, our data suggests Srpx2 colocalizes with white matter astrocytes, which will be explored further; inflammation and brain injury may be another way in which Srpx2 is involved in language and epileptic disorders. Conclusions: The expression pattern of Sprx2 in the mouse corresponds to structures involved in motor planning and the initiation of speech, as well as areas necessary for proper sleep regulation.