Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene

ANIL KUMAR CHAUHAN; Federico Andrea MORETTI; Alessandra IACONCIG; Francisco Ernesto Baralle; Andrés Fernando Muro

doi:10.1016/j.bbr.2005.02.020

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Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene

Journal article

Peer reviewed

Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene

ANIL KUMAR CHAUHAN, Federico Andrea MORETTI, Alessandra IACONCIG, Francisco Ernesto Baralle and Andrés Fernando Muro

Behavioural brain research, Vol.161(1), pp.31-38

2005

DOI: 10.1016/j.bbr.2005.02.020

PMID: 15904707

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Abstract

The extracellular matrix (ECM) plays an important role in the central nervous system (CNS) by modulating the migration of cells, axons and dendrites of neurons. Fibronectin (FN) is a major component of the ECM in the CNS and plays essential roles in development, cell adhesion and cell migration. Specific FN-isoforms, generated by alternative splicing at three conserved regions, the extra domain B (EDB), extra domain A (EDA) and type III homologies connecting segment (IIICS), have been shown to modulate these processes in vitro and in vivo. The inclusion of the EDA exon in the brain is highly regulated during development and aging, suggesting an important role of this exon in brain function. However, the direct role of FN-isoforms in brain function and behaviour is still obscure. Therefore, to directly assess the role of the FN-EDA exon in vivo, we have generated two mouse strains devoid of EDA exon regulated splicing in the FN gene that constitutively include (EDA+/+) or exclude (EDA−/−) the EDA exon in all tissues. Here, we show the behavioural consequences of the absence of regulated splicing of the EDA exon in the FN gene. Deletion of the EDA domain in the FN protein results in reduced motor-coordination abilities and vertical exploratory capacity, whereas mice that constitutively include the EDA domain displayed a decrease in locomotory activity in the open field (OF) test. These results strongly suggest that regulated splicing of the EDA exon is necessary for a normal function of the brain.

Fundamental and applied biological sciences. Psychology

Vertebrates: nervous system and sense organs

Biological and medical sciences

Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration

Details

Title: Subtitle: Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene
Creators: ANIL KUMAR CHAUHAN - International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy
Federico Andrea MORETTI - International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy
Alessandra IACONCIG - International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy
Francisco Ernesto Baralle - International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy
Andrés Fernando Muro - International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy
Resource Type: Journal article
Publication Details: Behavioural brain research, Vol.161(1), pp.31-38
Publisher: Elsevier Science
DOI: 10.1016/j.bbr.2005.02.020
PMID: 15904707
ISSN: 0166-4328
eISSN: 1872-7549
Language: English
Date published: 2005
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094546802771

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