Multiple alternatively spliced transcripts of the receptor tyrosine kinase MuSK are expressed in muscle

We have cloned and characterized five distinct mouse cDNAs encoding isoforms of MuSK, a receptor tyrosine kinase required for the development of the neuromuscular synapse. Comparison of the cDNA sequences with each other and with the mouse genomic sequence revealed that the cDNAs differ by the presence or absence of three alternatively spliced exons encoding an additional 10, 15 and 8 amino acids respectively. The location and sequences of these exons are conserved in MuSK cDNAs from different species. Examination of mouse genomic sequences revealed that the 15 aa exon sequence is present in a 52 bp exon with a non-canonical 3′ splice acceptor site at its 5′ end and an internal 3′ splice acceptor site consensus 45 bp downstream. Transcripts containing each of the alternatively spliced exons were detected in neonatal and adult mouse muscle, as well as in C2 myotubes. The presence of transcripts encoding MuSK isoforms with distinct extracellular domains in developing mouse muscle suggests that alternative splicing could potentially introduce additional complexity to the activity of MuSK in muscle.