A novel mouse model for developing therapeutic approaches of STXBP1 encephalopathy

Awardee: Mingshan Xue

Institution: Baylor College of Medicine

Grant Amount: $80,070

Funding Period: February 1, 2022 - January 31, 2023

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Summary:

STXBP1 encephalopathy is a severe neurodevelopmental disorder caused by heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1). Both protein haploinsufficiency and dominant-negative mutations were identified as the disease mechanisms. Models of haploinsufficiency have been developed and validated and are currently being used to test potential disease-modifying therapies. However, dominant-negative mutations may require therapeutic approaches that are different from those for haploinsufficiency. Mammalian models carrying dominant-negative mutations are currently lacking. Thus, this project aims to develop and validate a new mouse model carrying a dominant-negative missense variant to fill this critical gap. This model will provide a new tool for preclinical evaluations of different therapies of STXBP1 encephalopathy and lead to a better understanding of the disease pathogenesis.