Impaired motor coordination in mice lacking the EDA exon of the fibronectin gene.
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.
Chauhan
Anil Kumar
AK
International Centre for Genetic Engineering and Biotechnology, Mouse Molecular Genetics Group, Padriciano 99, 34012 Trieste, Italy. anil@icgeb.org
Moretti
Federico Andrea
FA
Iaconcig
Alessandra
A
Baralle
Francisco Ernesto
FE
Muro
Andrés Fernando
AF
D017398:Alternative Splicing / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology; D005091:Exons; D005106:Exploratory Behavior / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics*; D011596:Psychomotor Disorders / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D045442:Rotarod Performance Test / Q000379:methods; D013550:Swimming
D005353:Fibronectins; D012333:RNA, Messenger