Abstract
Lurcher (
Lc
) is a semidominant mouse mutant that displays a characteristic ataxia in the heterozygous state beginning in the third postnatal week. This symptom results from a neurodegenerative event in the cerebellum: There is a catastrophic loss of Purkinje cells in the heterozygote animal between postnatal days 10 and 15. In an effort to identify the genetic lesion borne by
Lc
mice, we initiated a cloning project based 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 called bacterial artificial chromosomes (BACs) that cover this region of mouse chromosome 6. These clones provided a good substrate for the isolation of markers that were used to refine the physical map of the locus. Furthermore, 20 of these markers were mapped onto our (B6CBACa-
A
w − J
/A − Lc
× CAST/Ei)F
1
× B6CBACa-
A
w − J
/A
backcross, refining the genetic map and identifying two nonrecombinant markers (
D6Rck354
and
D6Rck355
). 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 segment, 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.
[The
Lt1
sequence has been submitted to GenBank as two ESTs; the accession numbers are
U89356
and
U89357
.]