Genetic and physical delineation of the region overlapping the progressivemotor neuropathy (pmn) locus on mouse chromosome 13

The mouse autosomal recessive mutation progressive motor neuropathy (pmn) r esults in early onset motor neuron disease with rapidly progressing hindlim b paralysis, severe muscular wasting, and death at 4-6 weeks of age. pmn is thus considered a good animal model for motor neuron diseases and the char acterization of the causative gene should help in understanding the biologi cal causes of human spinal muscular atrophies. Here we report the generatio n of a physical map based on a high-resolution and high-density genetic map encompassing the pmn locus on mouse chromosome 13. We have positioned the pmn locus and a cluster of markers cosegregating with it within a genetic i nterval of 0.30 cM, delineated by two clusters of markers. We have construc ted an similar to 850-kb contig of BACs spanning the pmn critical region. T his BAC contig contains the breakpoint of synteny between mouse chromosome 13 and human 1q and 7p regions and lays the foundation for identifying at t he molecular level such a breakpoint region. The physical and genetic maps provided a support for the identification of five transcription units posit ioned in the nonrecombinant interval, and constitute invaluable tools for t he identification of other candidate genes for the pmn mutation.