GM1 Gangliosidosis: proposal of an animal model study using Danio rerio

• Grant number: 14/11891-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2015
• End date: April 30, 2017
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Carlos Eduardo Steiner
• Grantee: Carlos Eduardo Steiner
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Cláudia Vianna Maurer Morelli

Abstract

GM1 gangliosidosis is a rare autosomal disease caused by the deficiency of lysosomal enzyme ²-galactosidase, which is coded by the GLB1 gene. The enzimatic activity decrease leads to GM1 and GA1 gangliosides deposition inside the lysosomes. The disease is classified in three clinical types according to age of onset, enzymatic activity and severity. The Danio rerio (zebrafish) is an interesting animal model not studied yet for this disease. The zebrafish has well developed myelin sheath, similar to mammals, the peripheral nervous system has a swim and balance function, and alterations in myelin sheath can be identified by abnormal swim behavior. In addition, studies about the GM1 gangliosidosis in zebrafish could lead to a discovery of new GM1 ganglioside and ²-galactosidase enzyme functions, especially in the development beginning. In conclusion, this project aim to establish a model for functional studies of glb1 and glb1l genes in zebrafish, including gene knockdown using the morpholino technique and phenotype analysis by whole-mount in situ hibridization, histological analysis of myelin sheath, cartilages and bones, behavior analysis, and mobility test. (AU)