GIRK2 and neuronal pattern of generation and settling in homozygous weaver mice

Joaquín Martí^1,3, María C Santa-Cruz¹, Shirley A Bayer², José P Hervás^1,3

¹Unidad de Citología e Histología, Facultad de Biociencias, Universitat Autònoma de Barcelona, Campus Bellaterra, Spain; ²Laboratory of Developmental Neurobiology. Indianapolis, Indiana, USA; ³Both authors contributed equally to this work

Abstract: G-protein-activated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Several GIRK channel subunits have been found in the central nervous system. The weaver mutation has been identified as a single base-pair substitution in the gene encoding for a GIRK channel subunit, GIRK2. The cerebellum and the mesencephalon are predominately affected in the homozygous weaver mouse (wv/wv). In this article, we review our main findings about the patterns of cell generation, survival, and settling of two neuronal types in the wv/wv: Purkinje cells in the cerebellar cortex and dopaminergic neurons in the ventral midbrain. Moreover, we examine if the time of neuron origin determines the degree of cell vulnerability to the lethal action of mutated GIRK2. The possible involvement of other GIRK channel subunits is also considered within the context of earlier and more recent studies in the field.

Keywords: Purkinje neurons, dopaminergic neurons, GIRK2, weaver mouse, neurogenetic timetable