Project description
CHARGE syndrome (CS) is a rare genetic disorder affecting 1/10000 newborns. The symptoms of CS vary greatly from child to child and include a complex set of various medical and physical anomalies that gave it its name (Coloboma of the eye, Heart problems, Atresia of the choanae, Retarded growth and development, Genital anomalies, Ear abnormalities). Among these abnormalities, the retarded growth and development that is observed is related to autism spectrum disorders (ASD), including communication and socialization deficits, but this remains very poorly understood. Mutations in the Fam172a gene have been identified as being responsible for CS (Bélanger et al., PNAS 2018). Our lab has notably generated a mouse model with mutation of this gene which recapitulates all anomalies of the human pathology. However, although these mice clearly show behavioral problems (eg hyperactivity and aggression), these problems have not yet been characterized in detail. In addition, our lab identified Ago2 as an interaction partner of Fam172a, as well as a generalized disorder of alternative splicing as being responsible for the malformations observed in the Toupee model. Since alternative splicing is also known to play a major role in ASD, the general objective of this project is therefore to characterize in detail the Fam172a-Ago2 relationship, with particular emphasis on the regulation of alternative splicing and behavior problems in mutant mice for Fam172a.
Research team
Name: Saana Tork,Ph.D
Supervisor: Nicolas Pilon (UQAM)
Laureate: Doctoral scholarship 2022