Neurodevelopmental delay in the Cln3Δex7/8 mouse model for Batten disease

• Autor(a) principal: Osório, Nuno S.
• Data de Publicação: 2009
• Outros Autores: Marques, Maria Belém Sousa Sampaio, Chan, C-H, Oliveira, P., Pearce, D. A., Sousa, Nuno, Rodrigues, Fernando José dos Santos
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/64290
• topic: Aging; Animals; Brain; Child; Developmental Disabilities; Disease Models, Animal; Female; Genetic Predisposition to Disease; Genotype; Heterozygote; Humans; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Chaperones; Motor Skills Disorders; Neuronal Ceroid-Lipofuscinoses; Batten; CLN3; Genetics; Batten, CLN3, disease models, genetics, mousebehaviour, neurodevelopment, neuronal ceroid lipofuscinosis; mouse behaviour; Neurodevelopment; Neuronal ceroid lipofuscinosis; disease models; Ciências Médicas::Medicina Básica; Science & Technology

Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is a fatal inherited neurodegenerative disorder. The major clinical features of this disease are vision loss, seizures and progressive cognitive and motor decline starting in childhood. Mutations in CLN3 are known to cause the disease, allowing the generation of mouse models that are powerful tools for JNCL research. In this study, we applied behavioural phenotyping protocols to test for early behavioural alterations in Cln3(Deltaex7/8) knock-in mice, a genetic model that harbours the most common disease-causing CLN3 mutation. We found delayed acquisition of developmental milestones, including negative geotaxis, grasping, wire suspension time and postural reflex in both homozygous and heterozygous Cln3(Deltaex7/8) preweaning pups. To further investigate the consequences of this neurodevelopmental delay, we studied the behaviour of juvenile mice and found that homozygous and heterozygous Cln3(Deltaex7/8) knock-in mice also exhibit deficits in exploratory activity. Moreover, when analysing motor behaviour, we observed severe motor deficits in Cln3(Deltaex7/8) homozygous mice, but only a mild impairment in motor co-ordination and ambulatory gait in Cln3(Deltaex7/8) heterozygous animals. This study reveals previously overlooked behaviour deficits in neonate and young adult Cln3(Deltaex7/8) mice indicating neurodevelopmental delay as a putative novel component of JNCL.