Neurobiological effects of a null mutation depend on genetic context: Comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor

Hotfoot is a mutant mouse with an ataxic phenotype which has been shown to be due to a mutation in the Grid.? gene. In this paper, we compare molecula r, morphological, electrophysiological and behavioral features of two Grid2 alleles: Grid2(ho-4J) and Grid2(ho-Nancy) first show that these two mutati ons are deletions in the open reading frame of the gene and that no GRID2 p rotein is detectable in extracts of mutant cerebella, suggesting that the t wo alleles are null-like mutations. Morphological and electrophysiological analyses reveal no obvious differences between the two strains: both strain s showed the naked Purkinje dendritic spines and mismatch between the lengt h of the presynaptic active zone and postsynaptic differentiation character istic of the hotfoot mutation; and the same low level (20%) of multiple cli mbing fiber innervation of Purkinje cells was found in both strains. Only d ifferences in motor behavior were found between the two strains. The Grid2( ho-4J) mouse shows more severe ataxia that the Grid2(ho-Nancy) mouse and, a lthough both strains show a clear capacity to improve their performance of a motor task with training, the Grid(ho-4J) performance remains very poor w hereas Grid2(ho-Nancy) mice approach control levels. The only difference be tween the two strains is their genetic background. Our results show that the genetic background must be taken into account whe n analyzing sensorimotor performances of mutant mice. (C) 2001 IBRO. Publis hed by Elsevier Science Ltd. All rights reserved.