The rat Kalrn gene encompasses more than 65 exons spanning 600 kb of the rat genome, with at least six promoters and five 3'-terminal exons [26-28]. Alternative splicing yields multiple functionally different isoforms of rat Kalirin. We recently developed a mutant mouse specifically lacking the Kal7 isoform (Kal7KO) [17]; the 3'-terminal exon that encodes a PDZ binding motif known to interact with PSD-95 and AF-6 was eliminated [18,25]. Kal7KO mice show decreased anxiety-like behavior, impaired acquisition of a passive avoidance task, and abnormal behavioral and morphological responses to chronic cocaine [12,17]. A total Kalirin knockout mouse (T-KalKO) mice, in which exons 27-28 in the first GEF domain were replaced by a neomycin resistance gene, was also developed [29]. T-KalKO mice also display a number of neurological phenotypes. Use of these mouse models to clarify the role of Kalirin proteins in synaptic plasticity requires better characterization of the major products of the mouse Kalrn gene.
