The Lurcher mouse: Fresh insights from an old mutant

The Lurcher mouse was first discovered in 1954 as a spontaneously occurring autosomal dominant mutation that caused the degeneration of virtually all cerebellar Purkinje cells and most olivary neurons and granule cells. More recent molecular studies revealed that Lurcher is a gain of function mutation in the 82 glutamate receptor (GluR delta 2) that converts an alanine to threonine in the highly conserved third hydrophobic segment of GluR delta 2. The mutation converts the receptor into a constitutively leaky cation channel. The GluR delta 2 receptor is predominantly expressed in cerebellar Purkinje cells and in the heterozygous Lurcher mutant (+/Lc). Purkinje cells die due to the mutation in the GluR delta 2 receptor, while olivary neurons and granule cells degenerate due to the loss of their Purkinje cell targets. The purpose of the review is to provide highlights from 5 decades of research on the Lurcher mutant that have provided insights into the developmental mechanisms that regulate cell number during development, cerebellar pattern formation, cerebellar physiology, and the role of the cerebellum in CNS function. (c) 2005 Elsevier B.V. All rights reserved.