Splicing fibronectin's functions

On page 149, Muro et al. describe an elegant strategy for studying the functions of alternatively spliced isoforms of fibronectin. The work reveals surprisingly subtle phenotypes in mice that cannot carry out one form of alternative splicing, and demonstrates a general approach that could be applied to virtually any alternatively spliced gene.Disruption of the fibronectin gene in mice is lethal to embryos, making it difficult to analyze the developmental functions of the protein's isoforms. The authors got around this obstacle by inserting optimized splice sites and loxP recombination sites in the introns adjacent to the EDA exon of fibronectin. In mice homozygous for this allele, the EDA exon is constitutively included in fibronectin. Crossing this strain with a CRE recombinase– expressing “deleter” mouse produced animals lacking the EDA exon.

In wild-type mice, most of the embryonic fibronectin...