Employing a laser-captured microdissection (LCM), we have investigated the
somatic instability of CAG repeats in the variable brain cell lineage in th
ree patients with dentatorubral pallidoluysian atrophy (DRPLA). LCM enables
the isolation of single lineage brain cells for subsequent molecular analy
sis. We have found that CAG repeat size and the range of CAG repeats in the
cerebellar granular cells is smaller than those in cerebellar glial cells.
Similarly, those in the cerebral neuronal cells are significantly shorter
than those in cerebral glial cells. These data directly indicate that the C
AG repeat is relatively more stable in neuronal cells than in glial cells.
Furthermore, cerebellar granular cells show significantly smaller main CAG
repeat size and CAG repeat range than either Purkinje cells or cerebral neu
ronal cells, suggesting that somatic instability in the CAG repeat is marke
dly variable even among the different types of neuronal populations. The ce
ll-specific CAG repeat instability may thus be,more complex than has previo
usly been considered. LCM is a powerful tool for elucidating the mechanism
of the triplet repeat instability of each cell type.