Genomic Organization and Expression Analysis of the Mouse QkI Locus

qkI, encoding a KH domain-containing RNA binding protein, has been isolated as a candidate gene for the mouse neurological mutation quaking. Here, we describe detailed studies on its genomic structure and expression pattern. We isolated approximately 1 Mb of genomic region containing the quaking locus and determined its genomic organization. The qkI locus contains at least 9 exons spanning approximately 65 kb of DNA. It gives rise to six distinct transcripts encoding, theoretically, five different protein isoforms. Exons 1 through 4 are shared by all the transcripts, whereas coding exons and two distinct 3'-UTRs downstream to the exon 4 are differentially utilized. One isoform has a truncated KH domain and may act as an antagonist to the others. These findings and identification of a single transcription initiation site suggest that differential expression of each transcript is regulated by alternative splicing. Expression of each alternative transcript and protein product was also examined. Two types of transcripts, 5 kb-A and B, are most abundant in the brain of newborn mice and are gradually downregulated thereafter. In contrast, the other three messages, 6 kb, 7 kb-A and B, increase as myelination proceeds and peak at 2 weeks of age, corresponding to the most active stage of myelination. Although the qkI messages and their products are abundant in brain and heart, a lower level of expression was found in various other tissues tested. Alternative transcripts that share the same 3'-UTR showed very similar expression patterns, suggesting a regulatory role of the 3'-UTRs in qkI gene expression.