Various methods of substitution of Purkinje cells in a mouse model of olivocerebellar degeneration

摘要

Lurcher mutant mice represent a natural model of olivocerebellar degeneration (Phillips, 1960). They carry a mutation of the 52-glutamate receptor gene. Heterozygous individuals (+/Lc) suffer from complete postnatal loss of Purkinje cells and substantial decrease of cerebellar granular cells and inferior olive neurons. Purkinje cells die by apoptosis triggered by glutamate excitotoxicity resulting from the 82-glutamate receptor malfunction (Zuo et al, 1997). The death of granular cells and inferior olive neurons is secondary and is caused by the loss of the target of their axons - the Purkinje cells, The process of degeneration is finished by postnatal day 90, when no Purkinje cells are present in cerebellar cortex of Lurcher mutants and only 10 % of granular cells and 30 % of inferior olive neurons remain (Caddy and Biscoe, 1979).