Lurcher mouse

Abstract

Lurcher mutant mice represent one of the frequently used mouse models of the olivocerebellar degeneration. It is caused by a mutation in the γ2 glutamate receptor subunit encoding gene. The gain of function mutation changes the receptor into a leaky membrane channel leading to chronic depolarization of the cells expressing the receptor. Heterozygous Lurcher mice suffer from virtually complete postnatal loss of cerebellar Purkinje cells and reduction of granule, stellate and basket cells, and inferior olive neurons and relatively mild changes in the deep cerebellar nuclei. The death of Purkinje cells is a primary effect of the mutation and it shows features of apoptosis, autophagy, and necrosis. Extinction of the granule, stellate and basket cells, and inferior olive neurons is a target-related cell death. Lurcher mice display neurochemical and metabolic changes, abnormalities in the neurotransmitter and receptor systems, endocrine and immune abnormalities, and multiple behavioral deficits.