Defining the breakpoints of the quaking(viable) mouse mutation reveals a duplication from a Parkin intron

The quakingviable (qkv) mutant mouse shows a recessive neurological phenotype that includes central nervous system (CNS) dysmyelination, seizures, and tremor associated with voluntary movement. The molecular defect of qkv has been previously reported to be a spontaneous approximately 1 megabase (Mb) deletion in the proximal region of mouse chromosome 17 that occurred in the DBA mouse strain more than four decades ago. The mutation has recently been shown to affect three genes in the region: Quaking (qk), Parkin-coregulated gene (Pacrg), and Parkin. Here we determine the exact deletion breakpoints and demonstrate that the mutation is not just comprised of a approximately 1.1 Mb deletion, but also harbors a small 163 bp duplication fragment between the deletion breakpoints. Although the distal deletion breakpoint is within the fifth intron of the mouse Parkin gene, the duplicated sequence is derived from the sixth Parkin intron and shows positive transcriptional activity on a reporter gene in vitro. This complexity provides insight into a well-studied neurological mutant and may have a role in affecting the phenotype observed.