AN SIMILAR-TO-1.2-MB BACTERIAL ARTIFICIAL CHROMOSOME CONTIG REFINES THE GENETIC AND PHYSICAL MAPS OF THE LURCHER LOCUS ON MOUSE CHROMOSOME-6

Lurcher (Lc) is a semidominant mouse mutant that displays a characteri stic ataxia in the heterozygous state beginning in the third postnatal week. This symptom results from a neurodegenerative event in the cere bellum: There is a catastrophic loss of Purkinje cells in the heterozy gote animal between postnatal days 10 and 15. In an effort to identify the genetic lesion borne by Lc mice, we initiated a cloning project b ased on the position of the Lc mutation on mouse chromosome 6. We have extended our previous analysis of the genomic segment containing the Lc locus by isolating a set of stable and manipulable genomic clones c alled bacterial artificial chromosomes (BACs) that cover this region o f mouse chromosome 6. These clones provided a good substrate for the i solation of markers that were used to refine the physical map of the l ocus. Furthermore, 20 of these markers were mapped onto our (B6CBACa-A (W-J)/A - Lc x CAST/Ei)F-1 x B6CBACa-A(W-J)/A backcross, refining the genetic map and identifying two nonrecombinant markers (D6Rck354 and D 6Rck355). These two markers, in conjunction with the closest flanking markers, were used to identify a 110-kb genomic segment that contains all four markers and hence contains the Lc locus. This small genomic s egment, covered by multiple BACs, sets the stage for the final effort of this project-the identification of transcripts and of the mutation within the Lc locus.