High-resolution genetic, physical, and transcript map of the mnd2 region of mouse chromosome 6

The autosomal recessive mutation mnd2 is responsible for a lethal neuromuscular wasting disorder in the mouse. A high-resolution genetic map of the mnd2 region of mouse chromosome 6 was generated by analysis of 1147 F2 offspring from an intersubspecific cross between strains C57BL/6J-mnd2/+ and CAST/Ei. The results localize mnd2 to the 0.2-cM interval between D6Mit164 and D6Mit128. A contig of overlapping YAC, BAC, and P1 clones spanning the nonrecombinant interval was constructed. One novel gene isolated from the contig, D6Mm3e, is a new member of the WD repeat gene family. The observed gene order for the five positional candidate genes previously mapped to the region and five newly isolated genes is centromere-Hexokinase II-D6Mm5e-p62 Dok-Aup1-Rhotekin, D6Mm3e-Dynactin 1-Smooth muscle gamma actin-D6Mm4e-beta-adducin-telomere. Seven of these genes are located within the 400-kb nonrecombinant interval for mnd2. Comparison between wildtype and mutant failed to detect any differences in mRNA size, abundance, or coding sequence for these seven genes. The genes described here are positional candidates for the Parkinson disease susceptibility locus PARK3 that was recently mapped to the corresponding region of human chromosome band 2p13.1.